The colour reaction was stopped after 30 min and optical density was measured at 450 nm using an MRX Revelation plate reader from Dynex Technologies (Chantilly,

VA, USA). C-peptide was measured at (NLMDRL) 6 min after stimulation with 1 mg glucagon administered intravenously, as described previously [32]. All results for T cell and C-peptide are summarized as the mean, and measures of variability are reported as standard error (s.e.). Linear regression analysis was used to determine the best-fitted line, and an analysis of covariance was used to compare slopes between groups over the entire study. Metformin order Two-tailed Mann–Whitney U-tests were used to compare results at individual time-points between the treatment

groups. Two-tailed Wilcoxon matched-pairs signed-rank tests were used to compare results between individual time-points within the treatment groups. Demographic data, islet autoantibody and T cell responses to tetanus toxoid from patients treated with rosiglitazone and glyburide are shown in Table 1. No significant differences were observed in age, sex, race, body mass index (BMI), islet autoantibodies, tetanus responses or time since diagnosis between treatment groups at baseline or 36 months (Table 1). Islet-specific T cell responses in both patient groups increased during the first 12 months, becoming selleck increased significantly (P < 0·05) compared to baseline D-malate dehydrogenase at 9 months of treatment for both patient groups (Fig. 1). However, beginning at 15 months, T cell responses to islet proteins in the rosiglitazone-treated patients became suppressed significantly (P < 0·03). In fact, the T cell responses

to islet proteins in the rosiglitazone-treated patients became negative at 15 months (fewer than four blot sections) and remained negative throughout follow-up (Fig. 1). In contrast, the T cell responses to islet proteins in the glyburide patients remained positive throughout the study (Fig. 1). Mean stimulated C-peptide responses for both glyburide- and rosiglitazone-treated patients are shown in Fig. 2. During the first 12 months of follow-up, at the time T cell proliferation increased, the C-peptide in the glyburide-treated patients remained stable, whereas the C-peptide responses in the rosiglitazone-treated patients declined significantly (P < 0·05). However, after 12 months of follow-up, when islet-reactive T cell responses were suppressed in rosiglitazone-treated patients (Fig. 1), the C-peptide responses in the rosiglitazone-treated patients improved. In contrast, the C-peptide in the glyburide patients was observed to continue to decline throughout the study, reaching significance (P < 0·05) from baseline at 36 months (Fig. 2). Comparison of the glucagon-stimulated C-peptide responses for the rosiglitazone- and glyburide-treated patients demonstrated significant differences (P < 0·05) beginning at 27 months (Fig. 2).

Recombinant antigens Rv1733c, Rv2029c and Rv1886c (Ag85B) were recognized efficiently: 7/15 PPD+ donors recognized Rv2029c (CD4+: 15–97.2%, CD8+: 10.6–66.6%), 5/15 recognized Rv1733c (CD4+: 20.3–40%,

CD8+: 12.2–31.1%) and 4/15 recognized Ag85B (CD4+: 13.8–53.4%, CD8+: 12.6–97.7%). Corresponding to our previous observations, Rv2031c/hspX/acr was recognized by a minority of the donors (CD4+: 10.9–16.4%, CD8+: 42.7%) 7, 12. A substantial number of peptides was recognized by CD4+ and CD8+ T cells for Rv1733c (CD4+: 17/20 (10.1–76.9%) CD8+: 12/20 (10.4–100%)), Rv2029c (CD4+: 25/33 (10.4–100%) CD8+: 14/33 (10.3–66.6%)), Rv2031c (CD4+: 12/14 (10.2–53.8%) CD8+: 5/14 (11.3–42.7%)) and Ag85B (CD4+: 28/30

(10.1–75.3%) Wnt signaling CD8+: 25/30 (10.9–97.7%)). Some peptides were recognized by CD4+ T cells from more than one-third of the donors (e.g. 6/15 donors in case of Ag85B peptides 9 and 13, and 5/15 for Ag85B peptides 5, 6), whereas other peptides were recognized by CD4+ T cells in 4/15 donors, such as Rv1733c peptide 2 and Ag85B peptides 10, 12, 16 and 22. CD8+ T-cell responses were particularly observed against Rv1733c click here and Ag85B; these responses were found in four to five donors; Rv1733c peptides 17 (5/15), 2 and 19 (4/15), and Ag85B peptides 5 and 13 (4/15). Notably, some peptides were recognized by both CD4+ and CD8+ T cells (Rv1733c peptide 2, Ag85B peptides 5 and 13). Table 2 shows the cumulative

epitope recognition map for both CD4+ and CD8+ T cells in response to all tested proteins and peptides for all donors tested. Interestingly, the results suggest enrichment of epitopes in certain of immunogenic regions, for example Rv1733c(1–40), Rv1733c(161–200) and Ag85B(81–180), which harbor Rv1733c peptides 1–3, 17–19 and Ag85B peptides 5–14. The above-described Mtb DosR antigen-encoded peptide epitopes were recognized by donors with varying HLA genotypes. Many of the in vitro responses given in Fig. 4A and B matched with in silico epitope motif searches for the relevant HLA genotypes (data not shown) 35. This suggests that responses to Mtb dosR-regulon-encoded antigens occur in a wide range of HLA backgrounds. In order to better characterize the molecular interactions of Mtb DosR antigenic epitope presentation, we examined peptide recognition in the context of the highly frequent HLA-A*0201 genotype (New allele frequency database: http://www.allelefrequencies.net36) and found that Rv1733cp181–189 specific CD8+ T cells were able to lyse peptide loaded and endogenously processed Rv1733c-antigen loaded target cells in the context of HLA-A*0201 molecules (Supporting Information Fig. S2A and S2B). We have proposed that Mtb DosR-regulon-encoded antigens 7 that are expressed by Mtb during in vitro conditions mimicking intracellular infection represent rational targets for TB vaccination.

Methods: Using Western analysis and immunohistochemistry

we evaluated post mortem frontal cerebral cortex from patients with severe AD (mean age 76 years, range 66–91, n = 11, all male), and from control cases without serious central nervous system illness (mean age 77 years, range 61–95, n = 12, all male). We also examined brains of Tg2576 transgenic mice (males, aged 16–21 months), a model for chronic amyloid-induced brain injury. Results: Immunohistochemical labelling showed DAPK1 expression in cortical neurones of human cortex and axonal tracts within subcortical white matter, both in AD and in control IDH inhibitor brains. Western analysis confirmed DAPK1 expression in all samples, although expression was very low in some control cases. DAPK1 abundance in the AD group was not significantly different from that in controls (P = 0.07, Mann–Whitney test). In brains of Tg2576 mice DAPK1 abundance was very similar to that in wild-type littermates (P = 0.96, Mann–Whitney test). Conclusion: We found that DAPK1 was expressed in neurones of aged human frontal cortex,

both in AD and in control cases. “
“Recent evidence has placed Ibrutinib datasheet the unfolded protein response (UPR) at the centre of pathological processes leading to neurodegenerative disease. The translational repression caused by UPR activation starves neurons of the essential proteins they need to function and survive. Restoration of protein synthesis, via genetic Glycogen branching enzyme or pharmacological means is neuroprotective in animal models, prolonging survival. This is of great interest due to the observation of UPR activation in the post-mortem brains of patients with Alzheimer’s, Parkinson’s, tauopathies and prion diseases. Protein synthesis is also an

essential step in the formation of new memories. Restoring translation in disease or increasing protein synthesis from basal levels has been shown to improve memory in numerous models. As neurodegenerative diseases often present with memory impairments, targeting the UPR to both provide neuroprotection and enhance memory provides an extremely exciting novel therapeutic target. “
“R. Paudel, J. Hardy, T. Revesz, J. L. Holton and H. Houlden (2012) Neuropathology and Applied Neurobiology38, 520–534 Genetics and neuropathology of primary pure dystonia Neuropathology has been the key to understanding the aetiology of many neurological disorders such as Alzheimer’s disease, Parkinson’s disease, frontotemporal degeneration and cerebellar ataxias.

, 2003; Avonce et al., 2006; Cardoso et al.,

2007). It is tempting to speculate that A. baumannii trehalose production contributes to the organism’s ability to tolerate desiccation and thus may contribute to its transmission in the hospital setting. RT-PCR confirmed that members of the trehalose metabolic pathway are dramatically upregulated during stationary as opposed to exponential phase growth (Fig. 2). A hallmark of biofilm assembly is the transition from surface attachment to biofilm accumulation and maintenance. In that regard, our data also indicated that genes that are known to be associated with the initial stages of biofilm formation are check details predominantly expressed during exponential growth, whereas genes associated with biofilm maintenance are upregulated during stationary phase. More specifically, during the initial stages of A. baumannii biofilm formation, the csu operon is thought to modulate pili formation and, consequently, contribute to pilus-mediated attachment to abiotic surfaces (Tomaras et al., 2003). We found XL765 ic50 that two members of the csu operon, csuA/B (A1S_2218) and csuC (A1S_2215), as well as a putative pili assembly chaperone (A1S_1509), were upregulated during exponential phase of growth. Conversely, during stationary

phase of growth, putative members of the second messenger cyclic diguanylate (c-di-GMP; A1S-1949) and exopolysaccharide (A1S_1987) synthesis machinery were upregulated. In Pseudomonas aeruginosa, a close A. baumannii relative, c-di-GMP is hypothesized to play a role in the latter stages of biofilm formation. C-di-GMP augments biofilm maturation in two ways:

(1) it activates extracellular polysaccharide production, leading to a thickening of biofilm matrices, pentoxifylline and (2) it suppresses twitching motility and swimming (Tamayo et al., 2007). Collectively, these results indicate that exponential and stationary phase-induced ORFs would allow A. baumannii to initiate attachment to a surface, produce exopolysaccharide, and then mature into a hardy biofilm. Gram-negative bacterial secretion systems are responsible for the translocation of proteins across the double membrane. During exponential phase, a putative general secretion pathway protein (A1S_0269), with homology to type II secretion system (T2SS) proteins, was upregulated. Additionally, five loci from the Sec pathway were also induced; this pathway is essential in transporting proteins across the inner membrane before they can be excreted by the T2SS. In several bacterial species, including Vibrio cholerae and P. aeruginosa, the T2SS secretes toxins, proteases, phospholipases, and other virulence-associated proteins (Sandkvist, 2001). A putative type III effector protein (A1S_0390) was also induced during exponential phase of growth.

We note, however, that the proportion of inter-population variation differs depending on the genetic system: it is around 15% for allozymes,24 most DNA markers,22,23 and HLA-DPB1,25,49 and is slightly lower for the other HLA loci (∼ 10% on average), but is notably higher for GM (∼ 46%, including ∼ 39% among geographic groups and ∼ 7% among populations within geographic groups).12 This may be the result, in the

case of GM, of a bias in frequency estimation because of serological typing (as discussed above), although the effect of positive selection cannot be totally ruled out. In the case of HLA, we can conclude that balancing selection lowers inter-population variation although this effect is not find more very pronounced. Immunogenetics is therefore an informative tool in anthropology, despite the effect of natural selection, which is clearly demonstrated for HLA but appears to be weak. Moreover, the study of immunogenetic markers may provide important novel information for anthropological studies. Indeed, what is often considered to be a disadvantage in anthropological studies – a non-neutral mode of evolution of the studied polymorphisms – may

be highly relevant to understanding buy Seliciclib complementary aspects of human evolution, like environmental changes. Relevant results obtained through computer simulation have recently been obtained by Currat et al.,91 who estimated an unequal coefficient of selection for HLA-DRB1 in Southwest European (0·7%) and Northwest African (1·9%) populations separated by the Strait of Gibraltar. This difference can be seen as a genetic signature of heterogeneous environments in the past, i.e. different pathogen richness or prevalence of specific infectious diseases in the two regions. Also, the case of Amerindians would deserve deeper investigation to understand Tangeritin the evolution of their peculiar HLA genetic profiles. This could also be carried out by simulating different

scenarios taking into account both the initial settlement of America and its recent history marked by European colonization, which brought many new pathogens to this continent. The study of polymorphisms of important molecules for immune responses opens crucial areas of research in the field of human evolution, such as gene–pathogen co-evolution. This work received financial support from the Swiss National Science Foundation (SNF, Switzerland) grants no. 3100A0—112651 and 31003A—127465 (A.S.M.), the ESF (Europe) COST grant of Action BM0803 ‘HLA-NET’ (A.S.M.), the Oslo University Hospital Rikshospitalet, and Medinova (E.T.), and the US National Institute of Health Grant no. AI067068 (J.A.H. and S.J.M.). The authors declare no conflicts of interests.

In the latter model, both LXRα and -β isoforms were involved [48]. Yet, in this model, LXR activation reduced the expression of Skp2 and cyclin D1. Importantly, these effects were obtained with synthetic LXR agonists as well as with naturally occurring oxysterols. Similar results have also been reported in T- and B-CLL cell growth [29]. In T-CLL lines, Geyeregger et al. reported that LXR activation inhibits retinoblastoma protein phosphorylation and downregulates the expression of the cyclin B protein. In B-CLL cells, LXR activation was found to inhibit the expression of Bcl2 and MMP-9, thus reducing cell viability [29]

(Fig. 2A). The levels of circulating cholesterol were found to be higher n Lxra−/−Lxrβ−/− mice fed with a high-cholesterol diet than in BAY 57-1293 WT control mice. This resulted in cholesterol ester accumulation and development of prostatic intraepithelial neoplasia [49]. The accumulation of cholesterol esters, due to decreased expression of the transporter in charge of cholesterol efflux (i.e., ABCA1) and increased expression of the low density lipoprotein receptor in the absence of LXR

signaling, was linked to the increased expression of the histone methyl transferase enhancer of zeste homolog 2 . Enhancer of zeste homolog 2 increased the methylation of lysine 27 of histone H3 (H3K27) on the promoters of the tumor suppressor genes beta-microseminoprotein Doxorubicin cell line (Msmb) and homeobox protein NKX3.1 (Nkx3.1), whose expression turned out to be downregulated. The downregulation of the above-mentioned tumor suppressor genes, mediated by the accumulation of cholesterol esters in the absence

of LXR signaling, could be responsible for prostate tumorigenesis [49]. Differently from the previous model, LNCaP prostate Reverse transcriptase tumor cells stimulated with synthetic LXR agonists showed G1 to S-phase cell cycle arrest through the suppression of Skp2 [50], as reported for breast and colon cancer cells. Furthermore, LXR activation also promotes apoptosis of LNCaP cells through the disruption of the signaling mediated by lipid rafts [51]. This mechanism relies on the reduction of both membrane cholesterol content and phosphorylated fraction of AKT associated with lipid rafts. Of note, these effects are also active in vivo in immunodeficient mice xenografted with LNCaP cells and treated with synthetic LXR agonists [51]. In GBM, it has been shown that EGFRvIII promotes tumor survival through PI3K/sterol response element-binding protein-1-dependent upregulation of low density lipoprotein receptor (LDLR) [52]. The growth of GBM was inhibited in vivo by synthetic LXR agonist treatment, which caused inducible degrader of LDLR-mediated LDLR degradation and increased expression of the ABCA1 transporter [52].

The NKT cell activation was assessed in terms of the release of IL-2 which was measured by the CTLL assay as described in the literature 31. Briefly, supernatants were collected from the co-culture, serially diluted, and incubated

with 5×103 CTLL cells for approximately 40 h at 37°C. Then, 1 μCi of 3H-thymidine (Perkin Elmer, Waltham, MA, USA) was added for the final 16 h and cells were harvested and measured for 3H incorporation. This research was supported in part by NIH grant R21 AI078898 (K. J. S.). D. Z. is supported by MD Anderson Cancer Center and NIH grants R01 AI079232, a developmental award and a supplemental award from P30-AI36211. We thank the NIAID tetramer facility at Emory University, Atlanta, GA for providing PBS57-CD1d tetramers. A. N. C.

and K. J. S. wrote the paper. A. N. C. performed all experiments, analyzed the data and performed statistical MEK inhibitor analyses. P. T., S. S., and A. M. W. assisted with experiments. A. N. C., D. Z. and K. J. S. were involved in study design, analyzing and interpreting the data and checking the final version of the manuscript; the authors were fully responsible for content and editorial decisions for this manuscript. Conflict of interest: The authors declare no financial or commercial conflict of interest. “
“Members of the European Society for Immunodeficiencies (ESID) and other colleagues have updated the multi-stage expert-opinion-based diagnostic protocol for non-immunologists incorporating newly defined primary immunodeficiency diseases (PIDs). The protocol presented here aims to increase the

awareness of PIDs among doctors working in different fields. Prompt AZD2014 identification of PID is important for prognosis, but this may not be an easy task. The protocol therefore Leukocyte receptor tyrosine kinase starts from the clinical presentation of the patient. Because PIDs may present at all ages, this protocol is aimed at both adult and paediatric physicians. The multi-stage design allows cost-effective screening for PID of the large number of potential cases in the early phases, with more expensive tests reserved for definitive classification in collaboration with a specialist in the field of immunodeficiency at a later stage. In 2006, the Clinical Working Party of the European Society for Immunodeficiencies (ESID) published a multi-stage diagnostic protocol suitable for all doctors [1]. The protocol started from the clinical presentation of both paediatric and adult patients. Many primary immunodeficiency diseases (PIDs) present in childhood, but the most common clinically significant PID, ‘common variable immunodeficiency disorders’ (CVID), has a peak onset in the second and third decades of life. The multi-stage design allowed timely identification of potential PID by all doctors, while more costly elaborate tests were reserved for definitive classification at a later stage, in collaboration with an immunologist specialized in the field of immunodeficiency and a specialized laboratory.

Neutrophils play a central role in the host defense to pneumococcal infection by killing this bacterium (Musher et al., 1996). Therefore, we examined the effect of anti-TNF-α mAb on the recruitment of these cells in lungs. As shown in Fig. 1b, administration of this mAb led to the reduction in their number in BALF at 12 h after infection with S. pneumoniae, although there was not much difference in the number of macrophages and lymphocytes between anti-TNF-α mAb-treated and control rat IgG-treated groups. These results indicated that TNF-α was a key cytokine in the neutrophil-mediated host protective responses to this

infection. In order to characterize the role of TNF-α, its production was measured in BALF at various time intervals after infection Sirolimus ic50 with S. pneumoniae. As shown in Fig. 2, TNF-α showed an increase at 1.5 h, reached a peak level at 12 h and then declined to the basal level at 48 h. These results suggested that TNF-α may act for the host defense at a rapid stage of infection. To determine the cellular source of early TNF-α production in the infected lungs, the leukocyte fractions in BALF were followed at various time intervals postinfection. As shown in Fig. 3, BALF cells consisted

mostly of macrophages before infection, which showed a slight increase in their number at 1.5, 3 and 6 h postinfection. Neutrophils began to appear in BALF Belnacasan at 6 h and strikingly increased at 12 h. By contrast, lymphocytes slightly increased at 1.5, 3, 6 and 12 h postinfection, although the number was small. These results raised a possibility that neutrophils may play a certain role in the acute-phase production

of TNF-α in the infected lungs. This possibility was addressed by analyzing the intracellular TNF-α expression in neutrophils PDK4 in BALF in a flow cytometric analysis. As shown in Fig. 4a, BALF cells were set in the R1 and R2 lesions in the scattergram, and neutrophils were identified by the expression of a granulocyte marker, Gr-1. In the R1 lesion, Gr-1+ cells (Gr-1+ R1 cells) were detected only at 1.9% before infection, most of which showed the intracellular expression of TNF-α. This proportion increased gradually at 1.5 and 3 h and strikingly at 6 h, peaked at 12 or 24 h and then decreased at 48 h when TNF-α expression was attenuated as compared with that by 24 h. In addition to the R1 lesion, Gr-1bright+ cells expressing TNF-α appeared and increased in the R2 lesion (Gr-1bright+ R2 cells) at 6, 12, 24 and 48 h postinfection, although this population was hardly detected in the same lesion before and at 1.5 and 3 h. Gr-1dull+ cells that appeared and increased in the R2 lesion (Gr-1dull+ R2 cells), also expressed TNF-α at 12, 24 and 48 h postinfection. Similar results were obtained in the actual counts of Gr-1+ R1 cells, Gr-1bright+ R2 cells and Gr-1dull+ R2 cells that expressed the intracellular TNF-α synthesis (Fig.

In the reports by Gallina et al., graft overgrowth was observed in all transplanted patients and as early as 4 months after surgery. The latter tissue growth had virtually ceased 9–10 months after transplantation. Metformin molecular weight However, the grafts had enlarged aberrantly and were not confined to the surgical target sites. In fact, they encompassed regions of the white matter within the overlying cortex and ventral striatum. Hypermetabolic activity was demonstrated by FDG-PET 6–9 months after surgery but had decreased by 12 months after transplantation. Changes in D1 receptor binding varied between patients,

which correlated with limited improvement, if any [21,52]. One additional MRI report showed large cysts and well-delimited masses in one patient 10 years after transplantation [45]. The very first post-mortem study of a transplanted HD-affected brain was conducted in a patient who died 18 months after transplantation of causes unrelated to the procedure.

This study provided the initial proof of concept that solid foetal striatal grafts could survive in a human HD brain [42,53] (Table 3). In this find more patient, most grafts survived (six out of 10), with three localized in the right putamen, two in the left putamen as well as one in the anterior limb of the internal capsule. The majority of transplants could be identified macroscopically. Using immunohistochemical staining, the grafts exhibited a compartmentalized organization with the formation of striatal patchy areas known as p-zones, as well as areas lacking a striatal phenotype (non p-zones) [54]. Large and medium-sized neurones were predominantly seen in the p-zones of the grafts using typical striatal

markers such as dopamine receptor-related phosphoprotein 32 kDa (DARPP-32), calretinin, acetylcholinesterase (AChE), calbindin, enkephalin and substance P. Interneurones positively stained for choline acetyltransferase (ChAT), NADPH-diaphorase (NADPH-d) and parvalbumin were also detected within p-zones. Non p-zones were largely devoid of these markers but were richer in glial fibrillary acidic protein (GFAP)-positive astrocytes. Human leucocyte antigen-DR (HLA-DR), a marker for Amino acid macrophages and microglia, was rarely found in the transplant but was abundantly expressed in the host brain. There was no perivascular cuffing or T-cell infiltration, as visualized with CD4 and CD8. mHtt inclusions within the grafted tissue were not detected [42]. One additional case from the Freiburg University cohort provided a description of graft status at early time interval following transplantation [22] (Table 3). In that report, the authors confirmed the presence of three putaminal and two caudate grafts per hemisphere. DARPP-32-positive neurones, as visualized by immunohistochemistry, were found within the grafted tissue and were interspersed with calretinin- and somatostatin-positive interneurones.

We found that CXCL2 effectively restored neutrophil infiltration into the inoculated corneas and caused typical CaK in nude mice (Fig. 7). In fact, coadministration

of CXCL2 with blastospores exacerbated the severity of CaK and neutrophil infiltration in the corneas of BALB/c mice (Fig. 7). We compared the effect of IL-17 neutralization in mice concurrently inoculated with Candida in ear skin and the cornea. Contrary to its effect in cornea, IL-17 neutralization worsened the infection in skin (Fig. 8A). Histological analysis revealed check details that while IL-17 neutralization inhibited leukocytes infiltration at both sites, it led to fungal expansion in the skin (Fig. 8B and C). These results suggest that IL-17 inhibition elicits protective

and destructive responses in corneas and skin, respectively. The pathogenic role of lymphocytes in infectious keratitis has been previously reported in experimental models of other pathogens. Over three decades ago, it was noted that nude mice did not develop viral keratitis when challenged with the herpes Pifithrin-�� ic50 simplex virus [23]. Pearlman et al. showed that immunocompetent mice no longer developed Onchocerca volvulus keratitis when depleted of CD4+ cells [24]. By studying related mechanisms, Rouse and colleagues identified bystander activation of lymphocytes in the pathogenesis of herpes simplex keratitis [25, 26]. We report, for the first time, that CaK cannot be induced in either nude mice or CD4+ T-cell-depleted BALB/c mice, and that IL-17 is a critical factor in CaK initiation. We further showed that neutrophils and CD4+ T cells (supposed Th17 cells) are the main producers of IL-17

during CaK initiation (Fig. 4 and 5). On the other hand, Treg cells 2-hydroxyphytanoyl-CoA lyase and γδ T cells, which are key players in other systems [27, 28], were not involved in CaK formation in cornea (Supporting Information Fig. 2). Though the differential roles of these cell types in CaK and herpes simplex keratitis could be explained by the significant difference in the properties of the two pathogens, more extensive studies are needed to investigate why Treg cells and γδ T cells are not seemingly involved in pathogenesis of FK. Lastly, the differential effects of IL-17 neutralization on CaK and fungal dermatitis in the same mouse (Fig. 8) underscore the duality of IL-17 activity and the importance of cellular context in the pathogenesis of keratitis [29-33]. Thus, the effects of C. albicans may not be recapitulated by other fungal genera. While highlighting a critical role for IL-17 in CaK initiation, our results also bring to light several intriguing questions concerning corneal infections. The first involves the mechanism of efficient fungal clearance in corneas of nude mice. It has been proposed that structural features, as well as some innate factors, afford corneas the ability to hinder pathogens [34] or blastospore-pseudohypha transformation [35].