The innate immune response against Brucella in humans

Pathogens have developed different strategies to survive and multiply within their host. Among them is the ability to control phagocyte apoptosis while another is to affect the expression of cytokines which is necessary for a normal protective function of the immune response. To establish themselves and cause chronic disease in humans and animals, Brucella spp. invade and proliferate within monocytic phagocytes. We have established that in humans, Brucella suis impairs the apoptosis of monocytes and macrophages, thus preventing its host cell elimination. In mice, which are not naturally colonized by the bacteria, Brucella infection results in Type1 (Th1) cellular immune response which promotes a clearance of the bacterial organism. The development of this response is under the control of major cytokines like TNF-alpha, IFN-gamma and IL-12 produced at the onset of infection. We have observed that in humans, B. suis-infected macrophages which produce IL-1, IL-6, IL-10 and several chemokines including IL-8, do not secrete TNF-alpha. By constructing null mutants, we demonstrated that this inhibition involves the outer membrane protein Omp25 of Brucella, however the mechanism regulating the inhibition has not yet been clearly defined. It is likely that the Omp25-induced effect on TNF-alpha production assists bacterial evasion of antimicrobial defences at different levels. Firstly, by preventing the autocrine activation of macrophages thus inhibiting innate immunity and secondly by impairing the production of IL-12 and the development of a Th1 type specific immunity. In addition to the central role of the macrophage in Brucella infection, others cells of the innate immune response are recruited and influenced by the interactions between bacteria and host. For instance, human Vgamma9Vdelta2 T-cells play an important role in the early response to infection with intracellular pathogens. Evidence has been presented that their number dramatically increased in the peripheral blood of patients with acute brucellosis. We have shown that human Vgamma9Vdelta2 T-cells can be specifically activated by non-peptidic low molecular weight compound(s) from B. suis lysate or by soluble factors produced by B. suis-infected macrophages. Under these conditions, they produce TNF-alpha and IFN-gamma and reduce the bacterial multiplication inside infected autologous macrophages. This impairment of B. suis multiplication is due to both soluble factors released from activated gammadeltaT-cells (including TNF-alpha and IFN-gamma) and to a contact-dependent cytotoxicity directed against the infected cells. The interactions between the bacteria and these cells can counteract the intramacrophagic development of the bacteria and finally influence the further development of the host defense. We hypothesize that the chronicity or the elimination of the infection will depend on the balance between contradictory effects induced by the bacteria which favor either the host or the pathogen. Moreover, the interrelationship between the different cells must be taken into account in the analysis of the virulence of the bacteria and in the development of in vitro models of human macrophage infection.     

Aspects of the innate and adaptive immune responses to acute infections with BVDV

The immune response can be divided into innate and adaptive components that synergise to effect the clearance of pathogens. Recently, it has been realised that these arms of the immune system do not act independently, the magnitude and quality of the adaptive response is dependent on signals derived from the innate response. Here, we review the innate immune responses to bovine viral diarrhoea virus infections of cattle and relate these changes to immunosuppression and the subsequent development of the adaptive immune response.     

Viral deubiquitinases and innate antiviral immune response in livestock and poultry

Among many of the pathogens, virus is the main cause of diseases in livestock and poultry. A host infected with the virus triggers a series of innate and adaptive immunity. The realization of innate immune responses involves the participation of a series of protein molecules in host cells, including receptors, signal molecules and antiviral molecules. Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular or viral deubiquitinases (DUBs). DUBs have now been identified in diverse viral lineages, and their characterization is providing valuable insights into virus biology and the role of the ubiquitin system in host antiviral mechanisms. In this review, we briefly introduce the mechanisms of ubiquitination and deubiquitination, present antiviral innate immune response and its regulation by ubiquitin, and summarize the prevalence of DUBs encoded by viruses (Arteriviridae, Asfarviridae, Nairoviridae, Coronaviridae, Herpesviridae, and Picornaviridae) infecting domestic animals and poultry. It is found that these DUBs suppress the innate immune responses mainly by affecting the production of type I interferon (IFN), which causes immune evasion of the viruses and promotes their replication. These findings have important reference significance for understanding the virulence and immune evasion mechanisms of the relevant viruses, and thus for the development of more effective prevention and treatment measures.     

The bovine innate immune response during experimentally-induced Pseudomonas aeruginosa mastitis

Almost half of all clinical cases of mastitis are caused by Gram-negative bacteria. Among these bacteria, intramammary infection by Pseudomonas aeruginosa remains one of the most refractory to antibiotic therapy. The ability to recognize potentially harmful pathogens whether previously encountered or not, as well as the induction of an initial pro-inflammatory response to these pathogens, are critical components of host innate immunity. Although the innate immune response to another Gram-negative mastitis-causing pathogen, Escherichia coli, has been well-characterized, little is known about the response to other Gram-negative bacteria, including P. aeruginosa. The objective of the current study was to characterize the systemic and localized bovine innate immune response to intramammary infection with P. aeruginosa. The contralateral quarters of ten mid-lactating Holstein cows were challenged with either saline or P. aeruginosa. Following the establishment of infection, milk samples were collected and assayed for changes in cytokine and growth factor concentrations, complement activation, and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide (LPS)-binding protein (LBP), two accessory molecules involved in host recognition of Gram-negative bacteria. Initial increases in milk somatic cell counts were evident within 12h of experimental challenge and remained elevated for >or=3 weeks. Increased permeability of the mammary gland vasculature, as evidenced by elevated milk levels of BSA, was initially observed 20 h post-infection and persisted for 2 weeks. Within 32 h of challenge, increased levels of IL-8, TNF-alpha, IL-10, and IL-12 were detected, however, the elevated levels of these cytokines were not sustained for longer than a 24h period. In contrast, elevations in IL-1beta, IFN-gamma, TGF-alpha, TGF-beta1, TGF-beta2, sCD14, LBP, and activated complement factor 5 (C5a) were sustained for periods of >48 h. Systemic changes were characterized by elevated body temperature, induction of the acute phase protein synthesis of serum amyloid A and LBP, and a transient decrease in circulating neutrophils and lymphocytes. Together, these data demonstrate the capability of the mammary gland to mount a robust innate immune response to P. aeruginosa that is characterized by the induction of pro-inflammatory cytokines, complement activation, and increased levels of accessory molecules involved in Gram-negative bacterial recognition.     

Update on the role of innate immune receptors during Brucella abortus infection

The innate immune system constitutes an efficient defense mechanism against invading microbial pathogens. Recent studies have revealed the intracellular signaling cascades involved in the TLR-initiated immune response to Brucella spp. infection. However, there is a piece of the puzzle missing that is the role of non-TLR receptors in innate immunity. The involvement of TLR receptors in brucellosis has been investigated by different research groups. It was demonstrated that TLR2 clearly does not play any role in controlling Brucella abortus infection in vivo, whereas TLR9 has been shown to be required for clearance of this bacterium in infected mice. The participation of adaptor molecules, such as MyD88 and TRIF has also been discussed. Recently, we and others have reported the critical role of MyD88- and not TRIF-mediated signaling in dendritic cell maturation and in vivo resistance during B. abortus infection. However, the relationship between specific Brucella molecules and non-TLR receptors and signal transduction pathways needs to be better understood. It is now clear that the interaction between TLRs and recently identified cytosolic innate immune sensors is crucial for mounting effective immune responses. Finally, this review discusses the mechanisms used by Brucella to escape detection by the host innate immune system.     

The innate immune response of the bovine mammary gland to bacterial infection

Intra-mammary (IM) bacterial infection in cattle can result in clinical outcomes that range from being acute and life-threatening to those that are chronic and sub-clinical. The typical bacteria involved in IM bacterial infections activate the mammary immune system in different ways which can influence the severity of the outcome. A clear understanding of the mechanisms that activate and regulate this response is central to the development of effective preventative and treatment regimes. This review focuses on the different immune responses of the bovine mammary gland to common mastitis-causing pathogens. There is special emphasis on comparing the responses to Escherichia coli and Staphylococcus aureus infections, as these are typically associated, respectively, with acute/severe and chronic/sub-clinical forms of the disease.     

In utero heat stress alters the postnatal innate immune response of pigs

The effects of in utero heat stress (IUHS) range from decreased growth performance to altered behavior, but the long-term impact of IUHS on postnatal innate immune function in pigs is unknown. Therefore, the study objective was to determine the effects of early gestation IUHS on the immune, metabolic, and stress response of pigs subjected to an 8 hr lipopolysaccharide (LPS) challenge during postnatal life. Twenty-four pregnant gilts were exposed to thermoneutral (TN; n = 12; 17.5 ± 2.1 °C) or heat stress (HS; n = 12; cyclic 26 to 36 °C) conditions from days 6 to 59 of gestation, and then TN conditions (20.9 ± 2.3 °C) from day 60 of gestation to farrowing. At 12 wk of age, 16 IUHS and 16 in utero thermoneutral (IUTN) pigs were selected, balanced by sex and given an intravenous injection of LPS (2 µg/kg BW mixed with sterile saline [SAL] and injected at 2 µL/kg BW) or SAL (2 µL/kg BW). Body temperature was monitored every 30 min, and blood was obtained at 0, 1, 2, 3, 4, 6, and 8 hr following the LPS challenge. Blood samples were analyzed for glucose, insulin, non-esterified fatty acids (NEFA), cortisol, and cytokine concentrations. In addition, white blood cell counts were determined at 0 and 4 hr. Hour 0 data were used as covariates. Body temperature was increased (P < 0.01) in LPS (40.88 ± 0.08 °C) vs. SAL (39.83 ± 0.08 °C) pigs. Eosinophils tended to be decreased overall (P = 0.09; 43.9%) in IUHS vs. IUTN pigs. Glucose concentrations were reduced overall (P = 0.05; 5.9%) in IUHS vs. IUTN pigs. The NEFA concentrations tended to be greater (P = 0.07; 143.4%) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs tended to have greater (127.4%) circulating NEFA concentrations compared with IUTN-SAL and IUHS-SAL pigs. Cortisol was increased (P = 0.04) in IUHS-LPS compared with IUTN-LPS pigs at 3 hr (21.5%) and 4 hr (64.3%). At 1 hr, tumor necrosis factor α was increased (P = 0.01; 115.1%) in IUHS-LPS compared with IUTN-LPS pigs. Overall, interleukin-1β (IL-1β) and interleukin-6 (IL-6) were greater (P < 0.04; 281.3% and 297.8%, respectively) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs had increased IL-1β and IL-6 concentrations compared with IUTN-SAL and IUHS-SAL pigs. In summary, IUHS altered the postnatal cytokine, metabolic, and physiological stress response of pigs during postnatal life, which may have negative implications toward the innate immune response of IUHS pigs to pathogens.     

Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness: innate vs. adaptive immune response

REASONS FOR PERFORMING STUDY: Recent research has indicated that inflammation plays a role in the early stages of laminitis and that, similar to organ failure in human sepsis, early inflammatory mechanisms may lead to downstream events resulting in lamellar failure. Characterisation of the type of immune response (i.e. innate vs. adaptive) is essential in order to develop therapeutic strategies to counteract these deleterious events. OBJECTIVES: To quantitate gene expression of pro-inflammatory cytokines known to be important in the innate and adaptive immune response during the early stages of laminitis, using both the black walnut extract (BWE) and oligofructose (OF) models of laminitis. METHODS: Real-time qPCR was used to assess lamellar mRNA expression of interleukins-1beta, 2, 4, 6, 8, 10, 12 and 18, and tumour necrosis factor alpha and interferon gamma at the developmental stage and at the onset of lameness. RESULTS: Significantly increased lamellar mRNA expression of cytokines important in the innate immune response were present at the developmental stage of the BWE model, and at the onset of acute lameness in both the BWE model and OF model. Of the cytokines characteristic of the Th1 and Th2 arms of the adaptive immune response, a mixed response was noted at the onset of acute lameness in the BWE model, whereas the response was skewed towards a Th1 response at the onset of lameness in the OF model. CONCLUSIONS: Lamellar inflammation is characterised by strong innate immune response in the developmental stages of laminitis; and a mixture of innate and adaptive immune responses at the onset of lameness. POTENTIAL RELEVANCE: These results indicate that anti-inflammatory treatment of early stage laminitis (and the horse at risk of laminitis) should include not only therapeutic drugs that address prostanoid activity, but should also address the marked increases in lamellar cytokine expression.     

Impact of nutrition on the innate immune response to infection in poultry

Viral and bacterial diseases remain a threat to the poultry industry and countermeasures to prevent and control them are needed due to production losses. With the continued threat of exotic and emerging diseases and concern over the use of antibiotics in animal production, there is a serious and urgent need to find safe and practical alternatives to prevent or control pathogens. Identification of new tools for the design of new immunological interventions or therapeutic antimicrobials to reduce microbial pathogens in poultry is now required more than ever. Immunological interventions to reduce microbial pathogens in poultry would be of great value to the poultry industry and to the consumer. We have been advocating boosting immunity and encouraging the host to utilize its innate immune system to control and clear infections. Our research has addressed the use of innate immune mechanisms and components to develop new immune modulators (prophylactic and therapeutic) and the characterization and production of antimicrobial peptides as potential immune modulators in poultry. Dietary bioactive food components that interact with the immune response have considerable potential to reduce susceptibility to infectious diseases. With this premise, this paper asks and answers a series of pertinent questions on the utilization of avian immunity for increasing resistance to a variety of potential pathogens problematic in today's commercial poultry industry. Using experimental data to provide answers to these questions, we hope to stimulate a dialog between avian immunologists and nutritionists that results in coordinating and integrating their expertise into specific practical solutions that will benefit the industry and improve the well-being of commercial poultry.     

Porcine gammadelta T cells: possible roles on the innate and adaptive immune responses following virus infection

gammadelta T cells recognise different types of antigen in alternative ways to alphabeta T cells, and thus appear to play a complementary role in the immune response. However, unlike alphabeta T cells, the role or function of gammadelta T cells is still unclear. As pigs possess a high proportion of circulating gammadelta T cells, they are suitable large animal model to study gammadelta T cell functions. This as yet has not been fully exploited, leaving porcine gammadelta T cell biology and its role in immunity in its infancy. Foot-and-mouth disease (FMD) high potency "emergency" vaccines are able to induce early protection from challenge and it has been suggested that, in part, there is some involvement of innate immune responses. The antigen component of the vaccine is able to stimulate purified naive pig gammadelta T cells and induce the mRNA of various cytokines and chemokines. This observation suggests that gammadelta T cells probably contribute to the early phase of the immune responses to FMD vaccination, and perhaps infection. A subset of these circulating gammadelta T cells display a phenotype similar to professional antigen presenting cells and are able to take up and present soluble antigen to CD4(+) T cells in a direct cell-cell interaction via MHC class II. This direct interaction between gammadelta T cells and CD4(+) T cells is likely to have a significant influence on the out come of the adaptive immune response.     

Effects of midazolam on equine innate immune response: a flow cytometric study

Benzodiazepines (BDZ) are among the most frequently used class of psychotropic drugs employed in veterinary medicine in Brazil and worldwide due to their anxiolytic, muscle relaxant and anticonvulsant effects [J. Clin. Pharmacol. 33 (1993) 124]. Peripheral benzodiazepine receptor (PBR) sites were described in peripheral organs, endocrine steroidogenic tissues and immune organs and cells. Midazolam is a mixed-type agonist of PBRs. The present study is focused on the effects of midazolam on equine peripheral blood neutrophils, peritoneal macrophages and cortisol levels in plasma. Adult horses were treated with a single dose of midazolam (0.06 or 0.1 mg/kg) or with 0.9% NaCl. Immune cells were collected 24 h after treatment for flow cytometry analysis of Staphylococcus aureus-induced phagocytosis and oxidative burst. Plasma cortisol concentration was measured 30, 90, 180 and 360 min after midazolam treatment. Midazolam induced a dose-dependent reduction on: (1) peripheral blood neutrophil and peritoneal macrophage oxidative burst; (2) the capacity of both peripheral blood neutrophils and peritoneal macrophages to phagocyte S. aureus. Increments on plasma cortisol concentration were not found after 0.06 and 0.1 mg/kg of midazolam. The effects on oxidative burst of neutrophils and macrophages from horses treated with midazolam were interpreted as a consequence of an impairment of S. aureus-induced phagocytosis. The present data suggest that midazolam, most probably acting on PBRs present on equine macrophage and neutrophil membranes, might have changed some mechanisms related to both phagocytosis and oxidative burst. These results support the use of flow cytometry to identify functional properties and dysfunction of equine immune cells. They also confirm the notion that changes in the functional capacity of the immune system may represent an important hazard of exposure to drugs or chemicals.     

The innate immune response of equine bronchial epithelial cells is altered by training

Respiratory diseases, including inflammatory airway disease (IAD), viral and bacterial infections, are common problems in exercising horses. The airway epithelium constitutes a major physical barrier against airborne infections and plays an essential role in the lung innate immune response mainly through toll-like receptor (TLR) activation. The aim of this study was to develop a model for the culture of equine bronchial epithelial cells (EBEC) in vitro and to explore EBEC innate immune responses in trained horses. Bronchial epithelial biopsies were taken from 6 adult horses during lower airway endoscopy. EBEC were grown in vitro by an explant method. The innate immune response of EBEC was evaluated in vitro by treatment with TLR ligands. TLR3 is the most strongly expressed TLR at the mRNA level in EBEC and stimulation of EBEC with Poly(I:C), an analog of viral dsRNA, triggers a strong secretion of IFN-β, TNF-α, IL-6 and CXCL8. We further evaluated the EBEC innate immune response in horses that underwent a 4-month-training program. While training had no effect on TLR mRNA expression in EBEC as well as in bronchial biopsies, it increased the production of IFN-β after stimulation with a TLR3 ligand and decreased the secretion of TNF-α and IL-6 after stimulation with a TLR2 and TLR3 ligand. These findings may be implicated in the increased risk for viral and bacterial infections observed in sport horses. Altogether, we report a successful model for the culture of EBEC that can be applied to the investigation of pathophysiologic conditions in longitudinal studies.     

Porcine colon explants in the study of innate immune response to Entamoeba histolytica

Human amebiasis is caused by the protozoan Entamoeba histolytica. This protozoan is responsible for muco-hemorrhagic diarrhoea and liver abscess in affected populations. E. histolytica can be asymptomatic commensally confined to the intestinal lumen or can result in invasion of the colonic mucosa leading to ulceration and/or liver abscesses. Recently, human colonic explants have been identified as valuable in the study of host-parasite interactions. Here we investigated the potential of porcine colonic explants as an alternative to human tissues which are far less available. Porcine colonic explants were cultured with two strains of E. histolytica, one virulent (HM1:IMSS) and one avirulent (Rahman). Results from histopathological and real-time PCR analysis showed that porcine explants cultured with virulent ameba trophozoites react similarly to their human counterparts with an invasion of the tissue by the trophozoites and the triggering of typical innate immune response against the parasite. On the contrary, explants cultured with avirulent ameba trophozoites were preserved. The study open the way to the use of porcine colonic explants in the study of the complex interactions between the parasite and the host.     

玉米芯源低聚木糖对罗非鱼幼苗生长性能和先天免疫反应的影响

为研究玉米芯源低聚木糖对罗非鱼生长性能和先天免疫反应的影响,试验选取240尾罗非鱼幼苗随机分为4组,即对照组和试验1、2、3组,对照组饲喂基础日粮,试验组在基础日粮中分别添加0.5%、1%、2%的玉米芯源低聚木糖(CDXOS),试验为期8周。结果表明:与对照组相比,试验1、2组平均末重分别增加11.7%、20.4%(P<0.05),试验1、2、3组平均日增重分别增加13.0%、22.8%、11.2%(P<0.05),料肉比(F/U)显著降低9.0%、10.2%、8.4%(P<0.05)。试验1、2组溶菌酶(LSZ)活性较对照组分别增加66.6%、71.4%(P<0.05),超氧化物歧化酶(SOD)活性分别增加40.5%、67.8%(P<0.05),过氧化氢酶(CAT)活性分别增加22.8%、27.3%(P<0.05),丙二醛(MDA)浓度分别下降35.8%、42.6%(P<0.05)。综述,饲粮中添加玉米芯源低聚木糖能改善罗非鱼生长性能、促进先天性免疫反应,当添加量为1%时效果最为显著。     

肽聚糖在天然免疫中的作用研究

肽聚糖是细菌等原核生物细胞壁的特有成分,但它在天然免疫系统中的作用长期被低估。近年来的研究资料表明,肽聚糖识别蛋白是一类与肽聚糖结合的模式识别受体,可识别入侵细菌,激活相应的免疫反应,在免疫应答中发挥重要作用。随着对免疫机制研究的进一步深入,肽聚糖在医学、畜牧和生物工程等领域中的应用将会有更广阔的前景。     

Muscovy duck reovirus infection rapidly activates host innate immune signaling and induces an effective antiviral immune response involving critical interferons

Muscovy duck reovirus (MDRV) is a highly pathogenic virus in waterfowl and causes significant economic loss in the poultry industry worldwide. Because the host innate immunity plays a key role in defending against virus invasion, more and more attentions have been paid to the immune response triggered by viral infection. Here we found that the genomic RNA of MDRV was able to rapidly induce the production of interferons (IFNs) in host. Mechanistically, MDRV infection induced robust expression of IFNs in host mainly through RIG-I, MDA5 and TLR3-dependent signaling pathways. In addition, we observed that silencing VISA expression in 293T cells could significantly inhibit the secretion of IFNs. Remarkably, the production of IFNs was reduced by inhibiting the activation of NF-κB or knocking down the expression of IRF-7. Furthermore, our study showed that treatment of 293T cells and Muscovy duck embryo fibroblasts with IFNs markedly impaired MDRV replication, suggesting that these IFNs play an important role in antiviral response during the MDRV infection. Importantly, we also detected the induced expression of RIG-I, MDA5, TLR3 and type I IFN in Muscovy ducks infected with MDRV at different time points post infection. The results from in vivo studies were consistent with those in 293T cells infected with MDRV. Taken together, our findings reveal that the host can resist MDRV invasion by activating innate immune response involving RIG-I, MDA5 and TLR3-dependent signaling pathways that govern IFN production.     

Dynamics of innate immune response in Gallus domesticus using two methods of induced molting

The aim of this study was to compare the ability of laying hen abdominal macrophages during the second production cycle by using two different methods of induced molting. Two groups of Single Comb White Leghorn hens were induced to molt at the end of their first production cycle using feed restriction and ZnO supplementation. Macrophages were isolated from the abdomen and in vitro cytotoxic ability, at which point macrophage bactericidal moiety nitric oxide (NO) was recorded. Serum IgM and IgG titers against sheep red blood cells (SRBC) were determined at various stages: before molting (BM), 5% production level (5P), peak production stage (PP) and at the end of production (EP) level after fast and Zn-induced molt. Macrophages adherence percentage remained unaffected (p ≤ 0.05) during all production cycles, whereas the macrophage engulfment percentage and engulfment/cell was significantly higher (p ≤ 0.05) at PP in both fast and Zn-induced molted groups, as compared to all other studied stages. Macrophage NO production was increased (p ≤ 0.05) at PP and after SRBC and lipopolysaccrides (LPS) stimulus, when molted with ZnO supplementation. Serum total antibody titer against SRBC increased serum IgG and IgM titers during the second production cycle by Zn-induced molt. However, molting stress greatly reduced IgG and IgM production at the 5P stage. Serum Zn concentration increased with the onset of production but decreased at the EP stage irrespective of their molting regimes. Our results validate the strengthened innate and acquired immune response during the second production cycle after Zn-induced molting instead of fasting.     

A review of the interaction of Bacillus anthracis with cells of the innate immune response

Bacillus anthracis spores cause natural infections and can be used as biological weapons.The innate immune response is the first line of defence against invading pathogens and is likely to play a central role in this acute infection.To date the immune evasion mechanisms of B. anthracis are not well understood. Infection by inhalation with B. anthracis, the etiological agent of anthrax, is almost always lethal, yet cutaneous infections usually remain localized and resolve spontaneously in the majority of cases. Neutrophils are typically recruited to cutaneous but seldom to other forms of anthrax infections, raising the possibility that neutrophils kill B. anthracis. This is an overview of the interaction of B. anthracis with innate immune cells which also focuses on recent data on the role neutrophils play in anthrax pathogenesis. These data suggest that the timely recruitment of neutrophils can control the cutaneous and possibly other forms of B. anthracis infections and that the neutrophil granule proteins, a-defensins, play an important role in the potent anti-B. anthracis activity of neutrophils.