A number of studies suggested that Treg exert their suppressive function on effector T cells indirectly by modifying the function of antigen-presenting

dendritic cells. Interestingly, a recent in vitro study showed that LFA-1 is important for the formation of dendritic cell/Treg aggregates, because LFA-1−/− Treg were no longer able to inhibit the maturation of cocultured dendritic cells 20. Similar effects were also observed in a mixed human/mouse suppression system 21. We this website show here that LFA-1 deficiency results in a reduced Treg/effector cell ratio in the inflamed CNS. The reduction in Treg was already established in the spleen and thymi of unimmunized LFA-1−/− mice. Hence, besides a possible functional impairment of selleck compound Treg lacking LFA-1, these results indicate a more fundamental role for LFA-1 in generation of FoxP3+ Treg in the thymus. ICAM-1, a ligand of LFA-1, is expressed on thymic stromal cells 22. Therefore, LFA-1 potentially increases the

physical contact between thymocytes and stromal cells, resulting in enhanced T-cell receptor triggering. Increased T-cell receptor signaling during thymocyte selection favors the generation of naturally occurring Treg 23, which would explain the contribution of LFA-1 to the generation of naturally occurring Treg. So far, LFA-1 has been mainly recognized as a molecule regulating the migration of lymphocytes. Generally, the migration of LFA-1-deficient T cells to the peripheral lymph nodes is impaired, resulting in significantly smaller lymph nodes 10, 14. However, upon immunization with MOG-peptide, we observed that these differences in cellularity in lymph nodes between WT and LFA-1 KO mice are more or less levelled out (data not shown). In the context of EAE and transendothelial migration, Laschinger et al. 11 demonstrated that encephalitogenic dipyridamole T cells do not use LFA-1 for the initial adhesion to the endothelium of the blood/brain barrier. Instead, LFA-1 was involved in the later phases of migration into the CNS parenchyma. However, it should be noted that these results were obtained for the healthy spinal cord and that the role of LFA-1 for migration

could be different during later stages of an EAE disease, in which other integrin interactions may compensate for the lack of LFA-1. In our study, we did not directly address the question of lymphocyte migration via the blood/brain barrier. However, the observation that the frequency of MOG reactive CD4+ T cells in LFA-1−/− mice is already higher outside the CNS suggests an impaired suppression of effector T cells by Treg rather than an altered migration as cause for the higher ratio of effector versus Treg in the inflamed CNS in LFA-1−/−. Overall, the exacerbated EAE in the absence of LFA-1 seems to be due to the impaired suppression of autoantigen-specific effector T cells by Treg, which in LFA-1−/− mice show a more extensive expansion in secondary lymphoid organs upon immunization with the MOG-peptide.

Other techniques such as cyanoacrylates, fibrin glues, the Medtronic™ U-Clip®, and laser bonding have low levels of evidence supporting their use. Further research is required to establish any role for these techniques. © 2011 Wiley Periodicals, Inc. Microsurgery, 2012. “
“There is an increasing demand for successful free tissue transfer, with postoperative selleck products monitoring of flaps a key to early salvage. Monitoring methods have ranged from clinical techniques to invasive options, of which two are particularly applicable to buried flaps (Cook-Swartz Doppler probe and microdialysis). The evidence for these options has been represented largely in separate cohort studies,

with no single study comparing these three techniques. We aim to perform this comparison in a single cohort of patients. A prospective, consecutive cohort study comparing clinical monitoring, microdialysis and the implantable Doppler probe was undertaken. In 20 patients receiving 22 flaps, 21 flaps were monitored with microdialysis, 18 flaps with clinical observation, and 21 flaps with the Cook-Swartz Implantable Doppler probe. Exclusion was based on applicability and availability intra-operatively. Efficacy was assessed through selleck inhibitor sensitivity, specificity, positive, and negative predictive values. Nineteen of 22 flaps had no suspected anastomotic problems; 3 of 22 flaps were explored for anastomotic

problems, with two salvaged and one lost. The implantable Doppler and microdialysis were found to detect flap statistically earlier than clinical assessment, with microdialysis better at detecting flap compromise: 100% specificity (confidence GBA3 interval 31–100%) when compared to the implantable probe and clinical assessment

(67%: 13–98% and 33%: 2–87%, respectively). Each of the Cook-Swartz Doppler probe, microdialysis and clinical assessment was found suitable for monitoring in free tissue transfer. The implantable Doppler and microdialysis offer the potential for earlier detection of flap compromise. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014. “
“Local or distant metastatic recurrence after therapy is observed in 20–30% of cases of head-and-neck cancer. An unfavorable course may occur after cervical lymph node dissection due to loss of immunoprotective lymph nodes in the head-and-neck region. To overcome this problem, we performed autologous lymph node transplantation from the groin after head-and-neck cancer resection and cervical lymph node dissection. The patient was a 63-year-old man with squamous cell carcinoma in the mesopharyngeal lateral wall. After tumor resection and right cervical lymph node dissection, a lymph node-containing superficial circumflex iliac artery perforator flap was transplanted from the left groin. Pathological examination showed that cancer had invaded the primary tumor tissue stump. Thus, radiotherapy (66 Gy) was performed for the residual tumor from days 28 to 84 after surgery.

We compared gene expression profiles to the c2_all collection of curated gene-sets from the molecular signatures database (version 2·5) [35]. This collection contains gene-sets that are experimentally derived, as well as from expert curated pathway databases. A preranked file was created, containing the average difference between AA and SS for each probeset, sorted from most up-regulated in SS GSK126 in vitro to most down-regulated. We used the na28 annotation csv file from http://www.affymetrix.com to determine the gene symbol for each probeset and collapsed probesets to unique genes using the default, max_probe option, resulting in 18 600 unique genes. GSEA (version 2·0) [35] was run in preranked mode, using default

parameters (gene-set sizes between 15 and 500 leaving 1387 gene-sets, 1000 permutations, images on the top 50 gene-sets). We used mRNA extracted from distal colons obtained from four

SS and four AA mice for RT–PCR confirmation of our gene expression study. Reverse transcription to produce cDNA was performed using RT2 First Strand Kits (SA Biosciences, Frederick, MD, USA), according to the manufacturer’s instructions. RT–PCR was performed utilizing the LightCycler 480 real-time PCR system (Roche Applied Science, Mannheim, Germany) with RT2 SYBR green PCR master mix according, to the manufacture’s protocol (SA Biosciences). Predesigned primers for genes of interest (slpi, s100A8, lbp, CD68, IL18R1, IL33, ccl8, cxcl10, ccl12, buy BGJ398 pf4, ccl5, ccl7, fpr1 and ccr5) were obtained from SA Biosciences. For reference genes we evaluated three candidates, β-actin, β-glucuronidase and 18S rRNA. Beta-glucuronidase was selected based on similar expression patterns to most of our genes of interest and also because it was expressed invariantly between the groups. Hence, each

sample was normalized on the Adenosine basis of its β-glucuronidase content. Thermal cycling was performed as follows: initial denaturation at 95°C for 10 min, followed by 40 cycles of 95°C for 15 s and 60°C for 1 min. Each assay was performed in duplicate. The quantification points generated from quantitative RT–PCR (qRT–PCR) were normalized against a reference gene using this formula: normalized value of gene of interest with β-glucuronidase = 2–(QPGOI–QPRG), where QP = quantitative point, GOI = gene of interest and RG = reference gene (i.e. β-glucuronidase). We used the same 14 genes that we used for RT–PCR confirmation of our microarray study. We collected distal colonic samples from 3 days, 14 days and 28 days after the last (second) surgery. For each of the time-points we used four SS and four AA mice. The colons were collected, stored and processed for RT–PCR as described earlier. Group comparisons were analysed using the Mann–Whitney U-test with GraphPad Prism (Graphpad Software, San Diego, CA, USA). The differences were considered to be significant if P < 0·05.

Conclusions: RPGN if diagnosed early and treated aggressively

is salvageable. Early Renal biopsy is useful Alvelestat chemical structure in deciding treatment plan and prognostication. YAMANARI TOSHIO1, SUGIYAMA HITOSHI1, MORINAGA HIROSHI1, KITAGAWA MASASHI1, ONISHI AKIFUMI1, OGAWA AYU1, KIKUMOTO YOKO1, KITAMURA SHINJI1, MAESHIMA YOHEI1, OGAWA DAISUKE1,2, SHIKATA KENICHI1,3, OHMOTO YASUKAZU4, MAKINO HIROHUMI1 1Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; 2Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; 3Center for Innovative Clinical Medicine,

Okayama University Hospital; 4Otsuka Pharmaceutical Co., Ltd. Introduction: TFF3 plays essential roles in mucosal surface maintenance and reconstitution. A decrease in the urinary levels of TFF3 is associated with acute kidney injury in animal models. Circulating serum TFF3 is significantly increased PF 01367338 in patients with chronic kidney disease (CKD) in a recent report. However, whether the urinary levels of TFF3 are associated with renal dysfunction in patients with CKD is unclear. Methods: We analyzed the urinary TFF (uTFF) levels in spot urine samples from 216 patients with CKD, and assessed the relationships among the uTFF, proteinuria and kidney function. Patients were prospectively followed for three years for doubling of the baseline serum creatinine concentration Cyclooxygenase (COX) and the initiation of renal replacement therapy. Results: The excretion of uTFF3 significantly increased with the extent of albuminuria (P < 0.0001), urinary α1 microglobulin (P < 0.0001) and urinary β2 microglobulin (P < 0.0001) and the decline in the eGFR (P < 0.0001). A multivariate logistic regression analysis

showed that the patients with higher levels of uTFF3 were more likely to have CKD stage ≥G3b (P < 0.01). A longitudinal analysis demonstrated that patients with a higher uTFF3, in combination with macroalbuminuria, had a significantly worse renal prognosis (Log rank, P < 0.0001). The levels of urinary TFF3 in the renal end-point group were significantly higher than those in the renal survival group (P < 0.01). The AUC of uTFF3 for predicting the progression of CKD (0.879) was significantly higher than that of albuminuria (0.692) (P < 0.0001). The levels of uTFF1 and uTFF2 did not correlate with albuminuria. Conclusions: The excretion of uTFF3 is therefore significantly associated with albuminuria and a decline in the renal function. Moreover, the uTFF3 level can be used as a novel biomarker to predict the renal outcomes in CKD patients.

The late pre-B see more (fraction D) and immature B (fraction E) compartments had an approximately 40 and 50% decrease in numbers when compared to wild-type controls (p < 0.001 and p = 0.002, respectively). This pattern

of reduction in cell numbers matched that what we had previously observed at comparable stages of B-cell development on a BALB/c background [19]. However, unlike BALB/c IgHa.ΔD-iD mice where the absolute numbers of mature fraction F B cells in the bone marrow is halved when compared with those of wild-type; in C57BL/6 IgHa.ΔD-iD mice, the absolute numbers of fraction F B cells was fully normalized when compared with those from wild-type C57BL/6 control mice (p = 0.67) (Table 1). In order to distinguish between normalization of mature B-cell numbers due to the enhanced prevalence of B cells bearing IgM with charged, arginine-enriched CDR-H3s versus selection and increased survival for mature B cells that bear IgM with a more neutral CDR-H3 repertoire that could result from DH inversion or increased MK-1775 solubility dmso N addition (potential somatic

selection for “normality”); we evaluated 52 in-frame VDJCμ transcripts isolated from C57BL/6 ΔD-iD bone marrow fraction F B cells (Supporting Information Table 2). This permitted direct comparisons between the CDR-H3 loops of fraction F B cells using the same IgHa.ΔD-iD allele, but differing by C57BL/6 versus BALB/c genetic background. The pattern of reading frame usage, the prevalence of sequences lacking identifiable DH sequence, and the prevalence

of N addition was statistically indistinguishable between the IgHa.ΔD-iD repertoires expressed by the two mouse strains. Additionally, both the global prevalence of arginine, tyrosine, and valine in CDR-H3 and the relative distribution of CDR-H3 sequences containing one or more of these representative amino acids were statistically indistinguishable (Fig. 9A and B). The prevalence of neutral CDR-H3 loop sequences did not increase. To the contrary, the prevalence of highly charged and highly hydrophobic CDR-H3 loops in fraction F on the C57BL/6 background proved higher than on the BALB/c background (12.5% versus 9.2% and 3.8% versus 0; respectively) (Fig. 9C and D). We conclude that the normalization of IgHa.ΔD-iD fraction F B-cell numbers in C57BL/6 mice reflected an increase in the numbers Histone demethylase of mature, recirculating cells bearing both highly charged, arginine-enriched CDR-H3 loops and highly hydrophobic CDR-H3 loops (derived from alternative reading frames) when compared with those in BALB/c mice. Although the potential diversity of the CDR-H3 component of the immunoglobulin H-chain repertoire is astronomical, previous evaluation of the developing repertoire in BALB/c mice has allowed us and others to identify several key elements where there is strong evidence of either developmental or ontological constraints on this diversity (reviewed in [20]).

Strikingly, in these mice tumor burden was strongly reduced when compared to wild-type or p40−/−controls, arguing for a pro-tumorigenic role for IL-23, which was ascribed screening assay to a reduced

infiltration of cytotoxic CD8+ T cells into the tumor. Given the prominent function of IL-23 during the differentiation of Th17 cells, many researchers focused on the role of Th17 cells in tumor development, but contradictory results have been reported. While several groups attributed increased tumor-killing activity to Th17 cells in both subcutaneous and metastatic mouse melanoma models [103, 104], others have reported the opposite: in a transgenic model of spontaneous intestinal tumorigenesis, the lack of IL-17 abrogated tumor progression [105], and some metastatic melanoma models argue for a pro-tumorigenic function of IL-17 [106], which would fit the data obtained with p19−/−knockouts.

The general consensus seems to argue for tumor-promoting functions of both IL-23 and IL-17, if anything, but further work is needed to clarify their precise roles in anti-tumor immunity. Of note, the presence of GM-CSF has been shown to be beneficial in vaccination approaches during subcutaneous tumor growth [107]. Given that GM-CSF can be expressed https://www.selleckchem.com/products/LY294002.html in an IL-23-dependent fashion by CD4+ T cells, this might be another potential mechanism by which IL-23 can modulate tumor immunosurveillance. HSP90 The seemingly ubiquitous presence of IL-23 in inflammatory autoimmune disease models and its importance for the associated pathogenesis has significantly elevated the status of this cytokine. IL-23 has undoubtedly risen to prominence because of its unique ability to transform an activated T cell into an encephalitogenic, pro-inflammatory, and potentially self-harming effector cell. Indeed, IL-23 is perhaps the closest immunologists have come to identifying the “”magic bullet”" responsible for autoimmune disorders. This observation has already been translated into a successful clinical application, at least in the treatment of psoriasis. On the other

hand, the initial model of IL-23 only being implicated in the generation of Th17 cells has proven exceedingly (over) simplified. Not only does IL-23 induces a pathogenic T-cell program involving effector cytokines beyond the IL-17 family, but it also acts on additional innate cell types such as γδ T cells and ILCs. Furthermore, the regulation of IL-23 expression itself remains incompletely understood. As the complex network of IL-23-initiated cellular activity becomes more detailed, we will no doubt uncover more features of this cytokine governing the transition from antigen-specificity to auto-aggression. A.L.C. was supported by the EMBO long-term Fellowship ALTF-508–2011, and A.L.C. and F.M. by the Forschungskredit of the University of Zürich. B.B.

Finally, glycans from schistosomes are known to have a major role in the stimulation of innate immune responses [35]. We previously reported that the cytokine-inducing activity of 0–3 h RP is heat labile (declining at

temperatures above 50°C), and glycan dependent [8], with a key role for the mannose receptor [9]. Here we show that the production of all 3 cytokines assayed (IL-8, TNFα and IL-10) in WB cultures was reduced after 0–3 h RP was treated with sodium meta-periodate to disrupt the glycosylated moieties. This shows that glycans influence both pro-inflammatory and regulatory cytokine induction in S. mansoni-infected humans. MS-275 chemical structure However, as molecules released by the mature schistosome egg are also glycosylated [7], and as there is sharing of glycan moieties between different life cycle stages [36], it is possible that innate immune cells that respond to 0–3 h RP (e.g. through C-type lectins such as the macrophage mannose receptor) [9] are also responsive to antigens released by other parasite stages (e.g. the egg)[37], which maintain or down regulate cell responsiveness after initial parasite infection. Therefore, production of cytokines in response to cercarial glycosylated E/S material may be reinforced in response to egg deposition,

which may in turn feedback to affect the response to subsequent exposure to cercariae. It is also possible that the Th2-polarized adaptive response dominant after chronic infection in turn influence the Selleck AZD2014 ability of innate immune cells to produce IL-10 to cercarial E/S products. It is therefore likely that there will be ongoing communication, or crosstalk, between the innate and adaptive immune systems to regulate reactivity to both

Selleckchem Decitabine cercariae and eggs released by adult worm pairs. In conclusion, this study is the first to examine immune responses to cercarial E/S antigens, specifically the early production of cytokines indicative of the innate or early adaptive immune response, in human subjects. Our data show that cercarial E/S material induces the production of IL-10 in S. mansoni-infected individuals and suggests that cercarial E/S antigens are initial stimulants of a ‘regulated’ immune phenotype, which is prevalent after repeated and chronic infection with schistosomiasis. We gratefully thank the population of Diokhor Tack and the village chief, Daoure Mbaye, for their hospitality and participation in this study. This study would not have been possible without the field workers in Richard Toll, Abdoulaye Yague, Mankeur Diop, Moussa Wade and Ngary Sy, who assisted in the blood sample collection and microscopic analysis. We would also like to thank the medical and technical staff of the Health Centre in Richard Toll for their support. The authors would also like to thank Ann Bamford for help in preparation of antigen material. This study was supported by The European Union (EU INCO-CT-2006-032405 to APM, SM, and K P).

For the purposes of data analysis raw data replicates that were below the detection limit of the assay (ten copies) were given an arbitrary value of 1. Primers used are listed in Supporting Information Table 1. A total of 96-well polystyrene microtiter plates (Nunc, Roskilde, Denmark) were coated overnight at 4°C with 100 μL of antibody solution in 0.05 M carbonate buffer (pH 9.6) at 1 μg/mL. Subsequently, the plates were washed three

times with find protocol PBS (pH 7.2) +0.05% Tween 20 and blocked overnight at 4°C with carbonate buffer +2% BSA (pH 9.6). The serum samples were titrated by tenfold dilution from 1:10 to 1:10 000 in PBS+1% BSA and 0.2 % Tween 20, added to the wells and incubated for 1 h at room temperature. Following another wash with PBS (pH 7.2) +0.05% Tween 20 the plates were incubated for 1 h at room temperature with HRP-conjugated mouse anti-human IgG monoclonal antibodies DAPT clinical trial (BD Pharmingen, Brϕndhy, Denmark, Cat no. 555788) in 1:4000 dilution. Enzyme activity was assayed by incubation for 30 min at room temperature with 100 μL of tetra methyl benzidine (TMB) plus substrate per well. To stop the reaction, 100 μL of 0.2 M sulfuric acid was added, and the OD was measured at 450 and 620 nm for background subtraction. Comparisons between groups were assessed by the Kruskal–Wallis and Dunnett’s multiple comparisons test. The Mann–Whitney two-tailed t-test was used for analyses within groups. In all instances, a

p value <0.05 was considered significant. We would like to acknowledge Drs Gebeyehu Haile and Fekede Lemma from Hossana and Butajira hospitals for their contribution in the selection and screening of patients, Ato Alemayehu Kifle for bleeding and collecting specimens from these sites. We appreciate AHRI's administration for the support they provided when needed. The study was funded by EU INCO contracts ICA-CT-1999-10005, IC4-2001-10050, EU FP6 contract LSHP-CT-2003-503367 and the institutes' core budgets.

AHRI is supported by the governments of Ethiopia, Sweden and Norway. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. “
“The NF-κB/Rel family member c-Rel was described to be Reverse transcriptase required for the development of TH1 responses. However, the role of c-Rel in the differentiation of TH17 and regulatory CD4+Foxp3+ T cells (Treg) remains obscure. Here, we show that in the absence of c-Rel, in vitro differentiation of pro-inflammatory TH17 cells is normal. In contrast, generation of inducible Treg (iTreg) within c-Rel-deficient CD4+ T cells was severely hampered and correlated to reduced numbers of Foxp3+ T cells in vivo. Mechanistically, in vitro conversion of naive CD4+ T cells into iTreg was crucially dependent on c-Rel-mediated synthesis of endogenous IL-2.

Here, extracellular NFTs, a densely immunoreactive set of truncated-tau fibrils in the shape of a neuronal cell body were detected (Figure 5c, superior corner). Again, phosphorylation markers where able to detect a considerable number of phospho-NFT pathology, that is, NFTs and neurites around the affected areas (Figure 5a,b). When we quantified the total amount of structures per mm2 we observed an interesting fact, in advanced AD PD0325901 cases phosphorylation at sites Ser396–404 remains significantly increased when compared with phosphorylation at sites Ser199–202–Thr205 (Figure 5d).

While the total number of structures labelled by AT8 does not showed significant differences when compared with structures labelled by MN423 (Figure 5d). These data suggest that at some point the phosphorylation of tau protein at the sites Ser199–202–Thr205 stabilizes, while phosphorylation at the sites Ser396–404 remains dynamic. To further evaluate our finding of phosphorylation at sites Ser396–404 as one of the earliest Ibrutinib purchase events, we studied DS, which is also characterized by

phosphorylated tau protein. Here, in a similar way to AD, we found a large population of NFTs comprising phosphorylated tau (Figure 6a,b). The total number of NFTs per mm2 expressing phosphorylation at sites Ser396–404 was around 110 structures per mm2 (Figure 6h), a number quite similar to that seen during AD. Those structures were composed of tau phosphorylated at many sites; Ser396–404, Ser199–202–Thr205 and Ser262 (Figure 6a–d). To assess the status of C-termini of tau in those structures, single labelling using antibodies specific to early truncated tau (TauC3) and late truncated tau http://www.selleck.co.jp/products/Decitabine.html (MN423) was performed, and again, a considerable numbers of NFTs were detected with the cleavage at the D421 site (Figure 6e), whereas very few NFTs were detected with the cleavage at the E391 site (Figure 6f). In a similar way to the processing of tau protein during AD, PHF-1 immunoreactivity was able to detect early aggregates ‘NFT-like structures’

(Figure 6g, i and ii) as well as mature NFTs (Figure 6g, iii). Quantification analysis of all those structures revealed a similar pattern of events as seen during AD. The majority of NFTs were mainly composed of tau phosphorylated at sites Ser396–404, followed by phosphorylation at sites Ser199–202–Thr205. Sequentially followed by cleavage at site D421 (Figure 6h). To evaluate whether the evolution of the tangle was similar to what was seen during AD, we analysed the morphology of the NFTs seen during DS in terms of early aggregates and mature aggregates (criteria described earlier). Here we found that 80% of the NFTs labelled by pS262 were intracellular, while pSer396 and PHF-1 showed around 50% of iNFT and 50% of NFTs (Figure 6i). Again and similar to AD, AT8 marker showed that close to 70% of the structures where mature NFTs (Figure 6i).

trachomatis inclusions (Coers et al., 2008). This localization was observed only with C. trachomatis, while C. muridarum seems to have evolved mechanisms that prevent the accumulation of GTPases in the chlamydial inclusion, a possible immune evasion strategy (Coers et al., 2008). Although most of the assessed pathways seem to help the host cell in bacterial clearance, there is evidence that Chlamydiales also use TLRs to establish a replication-friendly environment. Chlamydia pneumoniae raises ATP levels through activation of the TLR2/Myd88 pathway. This behavior is crucial

because Chlamydiales are unable to produce ATP (Yaraei et al., 2005). MIP-2 and KC are two chemokines expressed upon Myd88 buy Ceritinib activation. In infected mice, these chemokines attract polymorphonuclear neutrophils to the lungs. Chlamydia pneumoniae is thought to use these cells to spread selleckchem throughout the lungs (Rodriguez et al., 2005). Immune cells can therefore be used as vehicles to reach new tissues instead of fighting the infection. Interaction of Chlamydiales with TLRs is of particular interest because they control inflammation that can become chronic or, if uncontrolled, cause damage. For example,

TLR2 recognition of bacterial PAMPs was linked to trophoblast apoptosis (Abrahams et al., 2004), which could provoke preterm delivery. Similarly, exposure to chlamydial Hsp60 (CHsp60) induces apoptosis in trophoblasts. Trophoblast TLR4 recognized CHsp60 and, through an unknown signaling pathway, induced several downstream caspases (Equils et al., 2006). Development of atherosclerosis was reduced in TLR2-deficient mice infected with C. pneumoniae. Without the TLRs, the level of circulating cytokines

was reduced and less dendritic cells were activated below (Naiki et al., 2008). Thus, different yet unknown chlamydial antigens seem to induce such a strong response that they cause severe damage to the surrounding tissue. Downstream of PRRs, there are not only cytokines and their receptors but also several enzymes that synthesize microbicidal molecules. ROS are strong microbicidals produced by macrophages, dendritic cells and neutrophils. Most of them are produced by NADPH oxidase (Nox), a multiproteic transmembrane complex. This family of genes is found only in multicellular organisms, with few exceptions (reviewed in Bedard & Krause, 2007). There are three different classes of NADPH oxidases (reviewed in Bedard et al., 2007). In most mammals, all seven genes are found, while rodents lack Nox5. The Nox present in phagocytic cells is Nox2. It is not clear whether other members of the Nox family are also specifically induced upon infection of phagocytic cells. Chronic granulomatous disease is a severe and debilitating disease found in individuals with mutations in components of the Nox2 complex.