The inability to formulate a unifying hypothesis is likely owing to the fact

that the processes behind maternal acceptance of the fetus are complex, multifactorial, and often compensatory.2–10 One approach to move the field forward is Osimertinib datasheet to incorporate insights gained from comparative studies of multiple mammalian species.11–13 For centuries, scientific study of the horse (Equus caballus) has contributed to the medical community’s understanding of anatomy and physiology.14 In recent years, studies of equine pregnancy have likewise advanced the fields of reproduction and immunology. As we discuss later, the horse is a natural model for immune recognition of the fetus. The pregnant mare demonstrates a clear immune response to placental alloantigens, thus addressing the central question of whether the mother is immunologically ignorant of, or tolerant to, her gestating fetus. This review

discusses the ways in which the horse has contributed to our understanding of pregnancy immunology and how equine research can advance the field. Here, we focus on the events of early pregnancy, as that is the period when there is abundant evidence for engagement and alteration of the maternal immune response. We first discuss the pertinent anatomical and physiological aspects of early horse pregnancy. We then discuss the concept of materno–fetal tolerance as it pertains to the horse. Finally, we describe resources that make high throughput screening compounds the horse a valuable species for the study of reproductive immunology and address pressing unanswered questions in our understanding of equine pregnancy. The equine placenta is characterized as diffuse and epitheliochorial, with six intact tissue layers between the maternal and fetal blood supplies.15 The majority of the interface between the uterus and placenta is formed by the tight apposition of the endometrial epithelium with the non-invasive trophoblasts of the allantochorion.16 This attachment occurs by the interdigitation of highly branched allantochorion villi with the Clostridium perfringens alpha toxin facing endometrium

to form microcotyledons. The microcotyledons, located near capillaries in the maternal and placental tissues, act as the primary units for nutrient exchange between mother and fetus.17 In this regard, the horse is similar to other species with epitheliochorial placentation, such as the pig. However, the equine placenta is distinguished by the specialized, highly invasive trophoblasts of the chorionic girdle. The chorionic girdle, first described in 1897,18 is so named because it forms a circumferential band around the developing conceptus (Fig. 1a,b). It is first visible at approximately 25 days of gestation, following the fusion of the allantois and chorion, which form the allantochorion membrane.

Foxp3+ Treg are functionally defined by their suppressive activity on effector T cells directed against foreign and self-antigens 21. The observed reduced Treg compartment of mice lacking cDC or selected

CD80/86 expression on cDC could hence render these animals prone to develop autoimmunity. Indeed, CD11c-DTA mice, which as shown above have a Treg deficiency, display the features of systemic lymphocyte activation, such as the accumulation of cells with memory T-cell phenotype (CD62LloCD44hi) (Fig. 3A), prevalence of Th17 and Th1 cells (Fig. 3B) and elevated IgG1, but not IgM serum titers (Fig. 3C). Notably, Ohnmacht et al. interpreted these findings as an indication of a general tolerance failure in cDC-less mice resulting in fatal autoimmunity 14. Furthermore, animals transiently depleted of cDC have also been reported

to display elevated IDH signaling pathway Th1 and Th17 cells, supporting the notion of impaired peripheral tolerance 13. In the latter study, the authors specifically suggested that these features result from the impaired Treg compartment of cDC-depleted animals 13. However, as we recently reported 15, CD11c:DTA Ibrutinib molecular weight mice that constitutively lack cDC also develop a progressive nonmalignant myeloproliferative disorder, driven by elevated systemic Flt3L levels. In the absence of measurable T-cell autoreactivity in DC-depleted mice 15, we hence had interpreted their above-mentioned features of lymphocyte activation, as consequences of the pathological systemic accumulation of myeloid cells, rather than as a result of a breakage of adaptive immune tolerance. Given our present finding that CD11c:DTA mice harbor an impaired Treg compartment (Fig. 1), we decided to revisit this

issue and investigate whether the Treg deficiency resulting from cDC ablation causes lymphocyte hyperactivation or autoimmunity. Specifically, Glycogen branching enzyme we took advantage of the fact that the above-mentioned [B7−/CD11c:DTA>wt] BM chimeras display a similar reduction of their Treg compartment, as DC- or B7-deficient animals, but due to the presence of CD80−/−CD86−/− cDC do not develop a myeloproliferative disorder (Fig. 4A). Importantly, [B7−/CD11c:DTA>wt] chimeras lacked all “autoimmune signatures” previously reported for CD11c:DTA and DTx-treated CD11c-DTR mice 13–15. This included the elevated frequencies of CD4+CD62LloCD44hi “memory” T cells (Fig. 4B), the increased prevalence of IFN-γ- and IL-17-producing cells (Fig. 4C) and the elevated IgG1 titers (Fig. 4D). These data thus establish that the “autoimmune signatures” of cDC-deficient mice are strictly associated with the development of the Flt3L-driven myeloproliferation and hence likely a consequence thereof. In support of this notion, we observed that a myeloid expansion induced by inoculation of WT mice with Flt3L-secreting tumor cells 22 also resulted in the accumulation of CD62LloCD44hi T cells (Fig. 4E).

Recent data obtained with mice lacking the

transcription factor BATF3 (Table 1) indicate that this need not always be the case. Batf3-deficient mice, particularly on a 129/Sv genetic background, exhibit a selective block in the development of CD8α+ DCs and CD103+ CD11b− DCs [28, Afatinib 29]. Notably, these mice display marked defects in the ability to mount cytotoxic T-cell responses to tumors and certain viruses, as well as in resisting parasites such as Toxoplasma gondii [28, 29]. Similarly, DT injection into Clec9a.DTR mice results in resistance to induction of cerebral malaria, probably because of a reduction in priming of Plasmodium-specific CD8+ T cells that induce pathology [29]. Finally, Langerin.DTR and DTA mice have revealed roles for LCs in immune responses and tolerance [14, 18]. Thus, the availability of mouse models for DC-subset depletion sheds light on the role of DC subtypes in immune regulation. CD11c.DTR and CD11c.DOG models are widely used to study the overall role

of DCs irrespective of subset. Importantly, both model systems display neutrophilia and monocytosis upon DT injection [18, 30]. This phenomenon had already been reported by Hochweller et  al. [9], but its functional implications have only recently begun to Metformin chemical structure be appreciated. For example, a recent study by Tittel et  al. [30] observed increased bacterial clearance in DT-treated CD11c.DTR and CD11c.DOG mice as compared with noninjected controls in a bacterial pyelonephritis model. This unanticipated result was not Cyclooxygenase (COX) because the presence of DCs restrained bacterial elimination. Rather, it appears to be a by-product of the rapid influx of neutrophils into the kidney upon DT injection. Both CD11c.DTR and CD11c.DOG mice exhibit two waves of neutrophilia: An “early” wave that is manifest 24 h after DT injection and a “late” wave beginning at 72 h after DT injection. The

“early” neutrophilia is due to the release of neutrophils from the bone marrow in response to chemokines CXCL1 and CXCL2 [30]. In contrast, the “late” neutrophilia is a consequence of increased granulopoiesis, likely caused by increased levels of Flt3L (fms-related tyrosine kinase 3 ligand), similar to what has previously been observed in CD11c.DTA mice (Table 1), which constitutively lack DCs [31, 32]. A new CD11c-based DTR mouse model (CD11c.LuciDTR, Table 1) generated by Tittel et  al. [30] exhibits the ‘late’ but not the “”early”" neutrophilia upon DT treatment. Although the mechanism remains elusive, these data imply that the “”early”" neutrophilia does not result from a direct interplay between DC function and neutrophil recruitment, but, rather, relates to the actual mouse model used to deplete DCs.

For this reason, most pathogens possess iron acquisition systems and are able to scavenge iron from the host. Genes for bacterial iron acquisition system are negatively

regulated by a ferric uptake regulator, Fur, and are derepressed under iron-depleted conditions (18,19). Thus, iron starvation is an important environmental signal leading to expression of iron acquisition systems and other virulence factors. Recently, a comprehensive transcriptional analysis revealed that iron starvation induces T3SS expression in B. bronchiseptica (25). We adopted a different approach, namely distinction of environmental signals in the culture medium rather than learn more the transcriptional profiling used in the former study (25). Our findings clearly support the conclusion that Bordetella www.selleckchem.com/products/PLX-4032.html T3SS is up-regulated under iron-starved conditions. Genome-wide microarray study of B. bronchiseptica has shown that expression of T3SS genes is up-regulated by growth phase progression, whereas expression of fhaB and cyaA genes is repressed in the stationary phase (26). During bacterial growth, the various environmental signals in bacterial

cultures change markedly in response to bacterial cell density, quorum sensing, and nutrient starvation. In Pseudomonas aeruginosa, T3SS and T6SS are inversely regulated by the RetS-mediated GacS/GacA two-component regulatory system (27). However, the precise mechanisms of the inverse regulation remain unknown. We found that the genes for type III secreted proteins and FhaB are inversely regulated in response to iron starvation, even though both genes are regulated by the BvgAS system (Fig. 2). It is tempting to speculate that the unknown repressor is expressed under iron starvation to shut down expression of certain virulence factors, including

FhaB. Further studies are necessary to elucidate the molecular mechanisms 5-Fluoracil purchase of BvgAS in response to the host environmental signal of iron starvation. This work was supported in part by the Ministry of Education, Culture, Sports, Science, and Technology of Japan through Grants-in-Aid for Scientific Research (B, 21390133; C, 23790484), for Scientific Research on Priority Areas (21022045) and for Japan Society for the Promotion of Science (JSPS) Fellows (23–7356). JK is a Research Fellow of the JSPS. The authors who have taken part in this study declare that they do not have anything to disclose regarding funding or conflict of interest with respect to the findings reported in this manuscript. “
“Plasmacytoid DC (pDC) secrete type I IFN in response to viruses and RNA/DNA/immunocomplexes. Type I IFN confer resistance to viral infections and promote innate and adaptive immune responses. pDC also produce cytokines and chemokines that influence recruitment and function of T cells and differentiation of B cells. Thus, pDC have been implicated both in protective immune responses and in induction of tolerance.

In an excellent review of measures of oxidative stress, Halliwell and colleagues

discuss more broadly the different measures of oxidative stress, including reasons leading to poor correspondence between markers, like the rapid metabolism of isoprostanes compared with the slower metabolism of oxidized proteins.51 Two major goals for controlling development of CKD are early detection and slowing progression to end-stage renal disease. Using oxidative stress biomarkers in a panel of biomarkers of processes known to impact on CKD development may allow early find protocol detection. Slowing its development is more problematic. Traditionally, inhibition of the renin-angiotensin-aldosterone system has been used to slow the progression of CKD,54 with established therapies relying on pharmacologic blockade of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. However, decline of GFR and elevated serum creatinine have continued in treated patients,55,56 and the need for novel treatments and interventions continues. Although the prophylactic use of anti-oxidant therapies in the treatment and amelioration of CKD is still in dispute, oxidant dysregulation occurs with age and age is one of the greatest risk factors for CKD. Some modifiable pathways and anti-oxidant treatments are summarized in Figure 2. There are many anti-oxidants that might be mentioned here,

but we have selected some that have some demonstrated benefits in CKD. Vitamin E comprises a family of eight different lipid-soluble tocopherols and Selleckchem Opaganib tocotrienols that scavenge free radicals by incorporating into the plasma membrane of cells, thus halting lipid peroxidation chain reactions.57 Vitamin E foodstuffs primarily consist of α-tocotrienol, which has a higher anti-oxidant efficacy; however, α-tocopherol has higher bioavailability in vivo than the other

seven compounds and so the focus has been on its usage. The basis of vitamin E supplementation is to enhance α-tocopherol levels in cell plasma membranes to prevent lipid peroxidation and resultant oxidative stress. Vitamin E is often delivered with vitamin Florfenicol C in an attempt to boost the anti-oxidant efficacy, as vitamin C has been shown to assist in recycling vitamin E. One drawback of α-tocopherol is that it takes several days of pretreatment to exhibit anti-oxidant effects.58 Trolox (±-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid), is an analogue of α-tocopherol that has shown far better free radical scavenging properties owing to its water solubility. The majority of in vivo studies using Trolox have reported beneficial effects in acute cases of renal injury such as ischaemia reperfusion, due to rapid solubility and increased potency.59 A combination supplement containing both α-tocopherol and Trolox may offer greater efficacy due to the fast-acting activities of Trolox combined with the sustained scavenging actions of α-tocopherol.

PBMC (4 × 105 cells/well in 100 µl) were incubated in duplicate with 5 µM of each peptide in complete medium with 50 UI/ml interleukin (IL)-2 (Boehringer, Mannheim, Germany) for 48 h. Plates were washed and 100 µl of polyclonal rabbit anti-human IFN-γ antibodies (Genzyme) diluted 1:250 were added. After overnight incubation at +4°C, plates were washed and 100 µl of polyclonal biotin-conjugated goat anti-rabbit IgG antibodies (Boehringer) diluted 1:500 were added for 2 h at 37°C. The plates were washed and incubated

with alkaline phosphatase-labelled extravidin (diluted 1/5000; Sigma-Aldrich Chimie SARL, Lyon, France) for 1 h. Chromogenic alkaline phosphatase substrate (Bio-Rad Laboratories, Hercules, CA, USA) was added to the wells

to develop spots. Blue spots Trichostatin A were counted with an automatic PLX4032 mw microscope (Zeiss Apparatus; Carl Zeiss, Göttingen, Germany). Negative controls were PBMC incubated in complete medium alone. Positive controls were obtained by activating PBMC with 50 ng/ml phorbol myristate acetate and 500 ng/ml ionomycin (Sigma-Aldrich Chimie SARL) (2000 cells/well). Only large spots with fuzzy borders were scored as IFN-γ-spot-forming cells (SFC). Responses were considered significant when the mean number of SFC by 106 cells in two experimental wells was superior to the highest either mean number of SFC in the negative control (PBMC alone) plus 3 standard deviations or number of SFC in the negative control (PBMC alone) plus 25 SFC/106 cells. HLA molecules were purified from human Epstein–Barr virus (EBV)-transformed cell lines by using affinity columns coupled to various immunoglobulins (Igs), as described previously [27,28]. After denaturation in urea plus NaOH, HLA heavy chains and β2m were separated from endogenous peptides then incubated with different concentrations of exogenous peptides (10−4–10−10 M)

and β2m. Reassembled HLA/peptide complexes were trapped in microtitration plate wells coated with anti-HLA monoclonal Igs, as described in Bourgault et al.[27]. Correctly folded HLA complexes were revealed Hydroxychloroquine research buy with alkaline phosphatase-coupled antiβ2m Igs (M28) with 4-methyl-umbelliferyl phosphate as a substrate (M-8883; Sigma-Aldrich Chimie SARL). Fluorescence was measured at 360/460 nm in a Microfluor reader (Victor 1420; Wallac, Turku, Finland). Results were expressed as the lowest peptide concentrations yielding a significant binding (20% of maximal fluorescence). Purification of HLA-DR molecules and peptide binding assays were performed as described previously [29,30]. These assays are specific for the HLA-DR molecules predominant in the European and North American populations, which are also frequent globally.

In 1965 Epstein and Maibach sensitized 13 psoriasis patients and 32 healthy controls with the strong allergen DNCB and found a slightly reduced sensitization ratio in the psoriatic group, but interpretation was hampered by the small study sample [15]. Two other experimental studies sensitizing psoriatic patients with DNCB have been conducted. Both studies used a high allergen dose for sensitization, sensitizing almost all participants, and hence they focused on the degree of challenge responses only. Moss et al. found reduced challenge reactions compared to healthy controls [5], and Obalek and co-workers reported a higher threshold in psoriasis patients compared to healthy

controls [6]. These results strongly suggest changes Afatinib price in the elicitation phase of sensitization among psoriatic patients. We only found a trend towards reduced reactivity in challenge responses. This might be due to the use of a different allergen or, more probably, that the effect is dependent upon the sensitization dose, which in our study was deliberately chosen to be relatively low, sensitizing only 65% of the healthy group in order to study the differences in sensitization potentials. A low sensitization ratio

of patients with diabetes type I compared with healthy controls was found in our buy SCH727965 study, although on the border of statistical significance. One study has demonstrated a reduced sensitization ratio in patients with rheumatoid arthritis using DNCB [7], indicating that the impaired reactivity to hapten could be common for autoimmune diseases. The autoimmune diseases psoriasis, diabetes type I, rheumatoid arthritis and inflammatory bowel Racecadotril disease have been linked through common clinical traits, genetic polymorphisms and immunological pathways [16–18]. Theoretically, it seems likely that the autoimmune diseases share an immunological milieu that can interfere with the expression of a contact allergic response. In contact allergy an individual becomes sensitized to a hapten, a low molecular weight chemical, through a complex process involving integrated signals from the innate and adaptive immune system, in which during the induction phase T cells are

primed in lymphoid organs, and upon re-exposure to the hapten during the elicitation phase are recruited to the skin and mediate the clinical outcome of allergic contact dermatitis. In murine studies, regulatory T cells have been shown to play a regulatory role in reducing the magnitude of the elicitation responses and in preventing priming to haptens [19–21]. In humans, specific CD4+CD25+ regulatory T cells capable of inhibiting CD4+CD25- nickel-specific effector T cells in vitro have been demonstrated in allergen-challenged skin and blood of non-allergic individuals [8,9], indicating an active down-regulation. These findings led us to investigate the elicitation sites of the participants in our sensitization study for down-regulatory mechanisms.

Altogether, this suggests high throughput screening assay that other mechanisms may have intervened. The expression or upregulation of various NKG2D ligands is tightly regulated in cells by stress, infections and transformation mechanisms. There is ample evidence of pathogens driving the diversity of NKG2D ligands. Numerous studies demonstrated

that viral infections increase the expression of NKG2D ligands but also that some viruses deploy evasive maneuvers to prevent expression of NKG2D ligands on the cell surface. The protein UL16 of human CMV binds to ULBP1, ULBP2, ULBP6 and MICB and retains these ligands intracellularly 28. Other intracellular mechanisms or signaling pathways induced by the presence of microorganisms can also influence NKG2D ligand expression. PR-171 concentration Notably, TLR signaling results in NKG2D ligand transcription. TLR4 engagement by LPS has been reported to upregulate cell-surface ULBP1 and MICA/B on human myeloid DCs and the expression of ULBP2 was induced by PolyI:C treatment 42. Moreover, various data have been reported in the infection with Mycobacterium tuberculosis. While the infection of DCs with a high MOI (2000) of this bacterium upregulates MICA surface expression 43, the infection of monocytes or macrophages with a low MOI (20) induces only the upregulation of ULBP1 expression 44. Thus, NKG2D ligand expression can be different from one infection to another, from one cell population

to another and their impact on the anti-infectious activity of Vγ9Vδ2 T cells could also vary. In conclusion, this study provides evidence that NKG2D can fine-tune the anti-infectious responses of Vγ9Vδ2 T cells against intracellular bacterium, through its interaction with its ligands. In addition,

it suggests that NKG2D could also be involved in the anti-infectious activity of Vγ9Vδ2 T cells against all microorganisms that have the ability to positively modulate NKG2D ligand expression. In a more general way, this study showed that T cells that do not utilize classical coreceptors, PtdIns(3,4)P2 such as CD4 and CD8, take advantage of other stimulatory molecules for a more efficient activation as well as for delivery of their effector functions, in this case a bactericidal one. Soluble ULBP1-LZ, ULBP2-LZ, UL16-LZ fusion proteins, M585 and M580 mAbs to human NKG2D and M15 anti-LZ mAb were a generous gift from AMGEN (Seattle, USA). HMB-PP was generously provided by J. L. Montero (Montpellier, France). Anti-ULBP1, ULBP2, ULBP3 and MICA/B mAbs were purchased unconjugated or as FITC- or PE conjugates from R&D Systems (Minneapolis, MN, USA). Anti-ULBP4 was purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Anti-mouse and isotypically matched control mouse Abs (conjugated or not) were all purchased from BD Biosciences (San Jose, CA, USA). Control or NKG2D siRNA were purchased from Dharmacon (Lafayette, CO, USA).

It is likely that if a place is found for Helicobacter spp. within IBD pathogenesis, other organisms

with similar traits may be equally able to fulfill the same role. Gradel et al. (2009) demonstrated recently that infection with https://www.selleckchem.com/products/pexidartinib-plx3397.html either Campylobacter or Salmonella predisposed to subsequent IBD development. We recently discussed the methodology utilized to identify the Campylobacter within this study, suggesting that further investigation may be warranted to define whether all Campylobacter attribute this risk or whether there are specific candidates (Hansen et al., 2010). Further exploration of the role that infectious triggers play in IBD in association with the host genetic factors involved may lead us to a better understanding of IBD, which may in turn take us far from the convenient, but imprecise labels of CD and UC. This may subsequently improve the accuracy of IBD research in much the same way that detailed genotyping and phenotyping of cancer variants has led to increased scientific accuracy of treatment studies and, as a result, the efficacy of cancer therapies. The other benefit of such understanding would, of course, be click here new therapeutic targets for IBD including perhaps immunization against

potential pathogenic triggers, targeted antibiotic therapies and probiotics designed to compete for the same ecological niche

as the pathogenic organism in question. We have recently come through a genetic revolution in our understanding of IBD. Perhaps the next revolution will be in understanding the colonic bacteria of IBD and both the route from ‘normal’ microbiota to dysbiosis, CYTH4 and the microbial factors that foster disease chronicity. Organisms from the genus Helicobacter may well be involved in both areas. The authors wish to acknowledge funding from the Broad Foundation, USA, and the Chief Scientist Office, Scotland. R.H. is funded by a fellowship from the Chief Scientist Office in Scotland. We declare no conflicts of interest with the data included in this manuscript. [Correction added 8 November after online publication: Acknowledgements section has been added]. “
“Mature lymphocyte immigration into the thymus has been documented in mouse, rat, and pig models, and highly increases when cells acquire an activated phenotype. Entrance of peripheral B and T cells into the thymus has been described in healthy and pathological situations. However, it has not been proposed that leukocyte recirculation to the thymus could be a common feature occurring during the early phase of a Th1 inflammatory/infectious process when a large number of peripheral cells acquire an activated phenotype and the cellularity of the thymus is seriously compromised.

This work was supported by grants from the EPZ-6438 order European Commission within the 6th Framework Programme, TB-VAC contract no. LSHP-CT-2003-503367 and the 7th Framework

Programme, NEWTBVAC contract no. HEALTH-F3-2009-241745 (The text represents the authors’ views and does not necessarily represent a position of the Commission who will not be liable for the use made of such information), the Bill and Melinda Gates Foundation, Grand Challenges in Global Health (GC6♯74, GC12♯82), the Italian Ministry for Instruction, University and Research (MIUR-PRIN to FD) and the University of Palermo (60% to F. D. and N. C.). Moreover, the authors gratefully acknowledge funding by BMN673 The Netherlands Organization for Scientific Research (VENI grant 916.86.115), the Gisela Thier Foundation of the Leiden University Medical Center and University of Leiden and the Netherlands Leprosy Relief foundation (grants ILEP 702.02.68 and 702.02.70). Conflict of interest: The authors declare no financial or commercial conflict of interest. See accompanying article: http://dx.doi.org/10.1002/eji.201040731 “
“Protective T-cell responses depend on efficient presentation of antigen (Ag) in the context of major histocompatibility complex class I (MHCI) and class II (MHCII) molecules. Invariant chain (Ii) serves as a chaperone for MHCII molecules

and mediates trafficking to the endosomal pathway. The genetic exchange of the class II-associated Ii peptide (CLIP) with antigenic peptides has proven efficient for loading of MHCII and activation

of specific CD4+ T cells. Here, we investigated if Ii could similarly activate human CD8+ T cells when used as a vehicle for cytotoxic T-cell (CTL) epitopes. The results show that wild type Ii, and Ii in which CLIP was replaced by known CTL epitopes from the cancer targets MART-1 or CD20, coprecipitated with HLA-A*02:01 and mediated colocalization in the endosomal pathway. Furthermore, HLA-A*02:01-positive cells expressing CLIP-replaced Ii efficiently activated Ag-specific CD8+ T cells in a TAP- and proteasome-independent manner. Finally, dendritic cells transfected with mRNA encoding Protein kinase N1 IiMART-1 or IiCD20 primed naïve CD8+ T cells. The results show that Ii carrying antigenic peptides in the CLIP region can promote efficient presentation of the epitopes to CTLs independently of the classical MHCI peptide loading machinery, facilitating novel vaccination strategies against cancer. “
“In paracoccidioidomycosis, a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb), studies have focused on the role of neutrophils that are involved in primary response to the fungus. Neutrophil functions are regulated by pro- and anti-inflammatory cytokines.