Cytokines and acute phase proteins associated with acute swine influenza infection in pigs

This study set out to investigate the cytokines and acute phase proteins (APPs) associated with the acute stages of experimentally-induced swine influenza virus (SIV) infection in 3-week-old, colostrum-deprived, caesarean-derived piglets. The piglets were inoculated intratracheally with 10^7.5 50% egg infective dose [EID₅₀] Swine/Belgium/1/98 (H1N1) SIV and were euthanased at time-points between 0 and 120 h post-inoculation (PI). Broncho-alveolar lavage fluid (BALF), lung homogenates and sera were examined for inflammatory mediators by bioassay or ELISA. Interferon (IFN)-α, interleukin (IL)-6, IL-1 and tumour necrosis factor (TNF)-α peaked in BALF 24–30 h PI, when virus titres and the severity of clinical signs were maximal.Whereas IFN-γ and IL-12, but not IL-18, increased in tandem in BALF, serum cytokine concentrations were either undetectable or were up to 100-fold lower. The APP C-reactive protein (CRP) and haptoglobin peaked 24 h later than the cytokines and reached higher levels in serum than in BALF. In contrast, lipopolysaccharide (LPS)-binding protein (LBP) only increased in BALF. Lung virus titres tightly correlated with BALF IFN-α, IL-6, IL-1, TNF-α, IFN-γ and IL-12, as well as with serum IL-6, IFN-α and IFN-γ. Signs of disease correlated with the same cytokines in BALF and serum, as well as with BALF LBP and serum CRP. The findings suggest that IFN-γ and IL-12 play a role in the pathogenesis of SIV and that APPs are induced by cytokines. This influenza infection model may have value in assessing the therapeutic potential of cytokine antagonists.     

神经介素B及其受体NMBR参与抗A型流感病毒H1N1亚型感染的信号通路

NMB/NMBR通过调节A型流感病毒（IAV/H1N1/PR8）感染诱导的细胞因子表达而参与抗IAV的先天性免疫反应。为探究其发挥抗IAV/H1N1感染的信号通路，本文用PR8和WSN毒株分别感染MLE-12细胞和小鼠，用NF-κB抑制剂BAY11-7028单独或联合NMB处理MLE-12细胞，小鼠后腿肌内注射NMB和NMBRA，采用RT-PCR和qRT-PCR分析NMB、NMBR、IL-6、IFN-α和NP基因表达变化，采用Western blot分析NMB、NMBR、P65/p-P65、IκBα和NP蛋白表达的变化。结果显示，BAY11-7028可促使PR8和WSN感染的MLE-12细胞中NMB、NMBR、IL-6和IFN-α基因表达水平均下降和NP基因表达水平上升，并降低NMB、NMBR和p-P65蛋白表达水平和提升IκBα和NP蛋白表达水平。然而，NMB联合BAY 11-7028诱导PR8或WSN感染后的细胞中IL-6和NP表达出现极显著下降和IFN-α显著上升。此外，NMB抑制PR8和WSN感染的小鼠肺组织内p-P65和NP蛋白表达水平和促进IκBα蛋白表达水平；NMBRA联合NMB抵消NMB对PR8或WSN感染后的这些蛋白表达水平的调节作用。综上表明，NMB/NMBR通过调节PR8和WSN感染的MLE-12细胞和小鼠体内的NF-κB信号通路上P65蛋白磷酸化和IκBα的表达，进而影响下游细胞因子IL-6和IFN-α基因的表达，从而发挥抗IAV/H1N1感染的先天性免疫应答反应。     

Rapid NK-cell activation in chicken after infection with infectious bronchitis virus M41

Natural killer (NK) cells are cytotoxic lymphocytes and play an important role in the early defence against viruses. In this study we focussed on NK cell and interferon (IFN) responses after infection with infectious bronchitis virus (IBV). Based on surface expression of CD107+, enhanced activation of lung NK cells was observed at 1 dpi, whereas in blood prolonged NK-cell activation was found. IFN-α and IFN-β mRNA and proteins were not rapidly induced whereas IFN-γ production in lung, measured by Elispot assay, increased over time at 2 and 4 dpi. In contrast, IFN-γ production in blood was highest at 1 dpi and decreased over time down to levels comparable to uninfected birds at 4 dpi. Collectively, infection with IBV-M41 resulted in activation of NK cells in the lung and blood and rapid production of IFN-γ and not IFN-α and IFN-β compared to uninfected birds.     

Differential expression of pro-inflammatory and anti-inflammatory cytokines during experimental infection with low or high virulence bovine viral diarrhea virus in beef calves

The objective was to compare the mRNA expression of pro-inflammatory (TNF-α, IL-1β, IFN-γ, IL-2, IL-12, IL-15) and anti-inflammatory (IL-4, IL-10, TGF-β) cytokines, after experimental infection with low or high virulence noncytopathic (ncp) bovine viral diarrhea virus (BVDV). Thirty BVDV-naïve, beef calves were intranasally inoculated with low (LV; n = 10, SD-1) or high (HV; n = 10, 1373) virulence ncp BVDV or with BVDV-free cell culture medium (Control, n = 10). Calves were euthanized on day 5 post-inoculation, and tracheo-bronchial lymph node and spleen samples were collected for mRNA expression through quantitative-RT-PCR. mRNA levels of pro-inflammatory (TNF-α, IL-1β, IL-2, IFN-γ) and anti-inflammatory (IL-4 and IL-10) cytokines were up-regulated in tracheo-bronchial lymph nodes of HV, but not in LV, compared to the control group (P < 0.05). IL-12 mRNA level was up-regulated in tracheo-bronchial lymph nodes of both LV and HV groups (P ≤ 0.05). A significant up-regulation of IL-15 mRNA was observed in tracheo-bronchial lymph nodes for LV calves (P < 0.002), but not for HV calves. Experimental inoculation with BVDV-2 1373 stimulated significant mRNA expression of pro-inflammatory and anti-inflammatory cytokines. In contrast, inoculation with BVDV-1a SD-1 only resulted in up-regulation of IL-12 and IL-15 mRNA, which is associated with activation of macrophages and NK cells during innate immune response.     

The influence of oral bacteria on tissue levels of Toll-like receptor and cytokine mRNAs in feline chronic gingivostomatitis and oral health

Feline chronic gingivostomatitis (FCGS) is an inflammatory disease of the oral cavity that causes severe pain and distress in affected cats. Treatment methods are currently very limited. The aims of this study were to assess the feline innate immune response by investigating the levels of cytokine and Toll-like receptor (TLR) mRNAs in tissue biopsies of cats with and without FCGS, and to relate this to the presence or absence of putative oral pathogens identified previously within these cats. Mucosal biopsies were collected from 28 cats with FCGS and eight healthy cats. The levels of TLR (TLR2, TLR3, TLR4, TLR7, TLR9) and cytokine (IL-1β, IL-4, IL-6, IL-10, IL-12, TNF-α, IFN-γ) mRNA was determined using quantitative PCR. In the FCGS group a statistically significant increase was seen in TLR2, TLR7, TNF-α, IFN-γ, IL-1β and IL-6 mRNA levels compared to the healthy group. In cats where Tannerella forsythia was present, statistically significant increases were seen in TLR2, TLR4, TLR7, TLR9, TNF-α and IL-1β mRNA levels compared to cats where this putative pathogen was absent. Statistically significant increases in mRNA expression were also seen in cats harbouring feline calicivirus (FCV) (TLR2, IL-1β, IL-6, IFN-γ) and Porphyromonas circumdentaria (TLR2, TLR3) compared to cats where these putative pathogens were absent. Pasteurella multocida subsp. multocida and Pseudomonas sp. did not significantly alter the expression of any TLR or cytokine mRNAs when compared to animals who tested negative for these species, while cats colonised with P. multocida subsp. septica demonstrated a statistically significant reduction in the expression of TLR7, TNF-α and IFN-γ mRNAs compared to cats free of this species. The expression of mRNA for several TLRs and cytokines is elevated in FCGS. A positive correlation was observed between clinical disease severity and the presence of FCV (p = 0.001; Rho = 0.58). Although the number of cats harbouring T. forsythia was low by comparison, 80% of samples in which it was present were from cases with the highest clinical disease severity. Positive correlations with clinical disease severity were seen for TLR2 (p = 0.00086), TLR7 (p = 0.049), TNF-α (p = 0.027), IFN-γ (p = 0.0015), IL-1β (p = 0.004) and IL-6 (p = 0.00001) mRNAs. The putative pathogens FCV and T. forsythia may be important in stimulating a host immune response to FCGS and may play a role in the pathogenesis of this disease.     

Rough virulent strain of Brucella ovis induces pro- and anti-inflammatory cytokines in reproductive tissues in experimentally infected rams

The ovine brucellosis caused by Brucella ovis has tropism for reproductive tissues but until now the mechanism of bacterial persistence is not understood. Cytokine expression profiles were studied for 8 months in rams after being experimentally infected with the rough virulent strain of B. ovis (R-B. ovis) to study the pathogenesis of B. ovis and immune mechanism possibly associated to bacteria tropism and persistence. The messenger RNA (mRNA) expression levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-10, IL-12, interferon-γ (INF-γ) and tumour necrosis factor-α (TNF-α) cytokines were quantified by real-time quantitative RT-PCR (qRT-PCR) in reproductive tissues (epididymus, testicles, ampolae, vesicular glands and bulbourethral glands), and non-reproductive (liver, spleen and kidneys) tissues at 30, 60, 120 and 240 days post infection (dpi). During the acute phase of infection at 30 dpi, the host immune response was most notable demonstrating an up-regulation of several cytokines in reproductive tissues, including the epididymus (IL-6, IL-1β and IL-1α), testicles (INF-γ and IL-12), bulbourethral glands (IL-6 and TNF-α) and ampolae (INF-γ, IL-10, IL-1β and IL-1α). During the development of infection, cytokine gene expression levels decreased, providing evidence of immunosuppression and evidence of immune evasion that favoured persistence of chronic R-B. ovis infection. During the chronic phase of R-B. ovis infection (120 and 240 dpi), cytokine production was down-regulated in the epididymus (IL-1β and IL-1α), testicles (INF-γ and IL-12), and ampolae (INF-γ, IL-10, IL-1β and IL-1α), with the exception of the bulbourethral glands (IL-6 and TNF-α) and epididymus (IL-6); in these tissues, R-B. ovis infection resulted in up-regulation of the pro-inflammatory cytokine IL-6. Herein, we report cytokine expression profiles in tissues of rams experimentally infected with the rough strain of B. ovis, which are associated with bacterial persistence and macrophage activation.     

Differential gene expression of proinflammatory chemokines and cytokines in lungs of ascites-resistant and -susceptible broiler chickens following intravenous cellulose microparticle injection

Intravenous injection of microparticles (MPs) is a tool to reveal susceptibility to pulmonary hypertension (PH) syndrome (PHS, ascites) in broilers. After injection MPs get lodged in pulmonary arterioles and cause localized inflammation. To examine the expression of chemokines/cytokines during the MP-induced pulmonary inflammatory response, lungs were collected from 4-week-old broilers (6/line/time point) from the PHS-resistant (RES) and -susceptible (SUS) broilers before (0 h) and after (2, 6, 12, 24, and 48 h) MP injection and analyzed using quantitative RT-PCR. In both lines, expression of interleukin-1β (IL-1β), IL-6, IL-8, and K60 increased from 0 to 6 h, reached peak levels at 6 and 12 h, and decreased thereafter, whereas IL-4 and interferon gamma (IFN-γ) expression remained elevated past 12 h. Lungs from the RES line broilers had higher expression (P < 0.05) of IL-1β and IL-6 at 2, 6, and 12 h; higher IL-8 at 6 and 12 h; higher K60 at 6, 12, and 24 h; higher IL-4 at 12, 24, and 48 h and higher IFN-γ expression at 6 and 48 h post-MP injection than SUS line broilers. Higher expression of chemokines/cytokines in RES compared to SUS line lungs may explain the ability of RES line broilers to effectively counteract the MP-induced PH and resolve the vascular occlusion.     

β-羟丁酸抑制脂多糖诱导奶牛中性粒细胞核因子-κB信号通路的激活

高酮血症造成奶牛中性粒细胞先天免疫机能受到抑制,本研究探讨β-羟丁酸(BHBA)是否抑制脂多糖(LPS)诱导的奶牛中性粒细胞核因子-κB(NF-κB)信号通路的激活。分离健康奶牛中性粒细胞,采用LPS(100 ng/mL)和不同浓度(0.5、1.0、2.0和4.0 mmol/L)BHBA作用于中性粒细胞,收集细胞,应用实时荧光定量PCR(qRT-PCR)检测中性粒细胞中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和NF-κBp65 mRNA表达水平,Western blot检测NF-κBp65蛋白表达水平,比色法检测核因子-κB抑制物激酶β(IKKβ)激酶活性,酶联免疫吸附试验(ELISA)法检测促炎细胞因子TNF-α、IL-6和IL-1β的分泌量。结果表明:与对照组(不进行BHBA和LPS处理)相比较,LPS组(单独LPS处理)中IL-1β、IL-6、TNF-α和NF-κBp65 mRNA表达水平和NF-κBp65蛋白表达水平极显著增加(P <0.01),IKKβ激酶活性极显著增强(P<0.01),IL-1β和TNF-α的分泌量极显著增加(P<0.01),IL-6的分泌量显著增加(P <0.05)。与LPS组相比,0.5、1.0、2.0和4.0 mmol/L BHBA均使IL-1β、IL-6、TNF-α和NF-κBp65 mRNA表达水平和NF-κBp65蛋白表达水平显著或极显著增加(P<0.05或P<0.01),IKKβ激酶活性显著或极显著增强(P<0.05或P<0.01),IL-1β、IL-6和TNF-α的分泌量显著或极显著增加(P<0.05或P<0.01)。以上结果表明,高浓度BHBA可以抑制LPS诱导的奶牛中性粒细胞NF-κB信号通路的激活,具有一定的抗炎功能。     

重组RTB蛋白对巨噬细胞活化及对NF—κB信号通路的影响

采用重组RTB蛋白刺激RAW264．7细胞,对iNOS、IL-6和TNFJamRNA表达及IκB-α和NF-κBp65磷酸化蛋白表达进行分析,探讨重组RTB蛋白对巨噬细胞活化及对NF-xB信号通路的影响。结果显示,重组RTB蛋白组RAW264．7细胞iNOS、IL-6和TNF—αmRNA的表达显著高于对照组（P〈0．01）,并呈现时间和计量依赖性;加入NF—κB抑制剂BAY后,iNOS、IL-6和TNF0amRNA表达降低（P〈0．05或P〈0．01）。随RTB刺激RAW264．7时间的延长,IκB-α蛋白的磷酸化程度增强,NF-κBp65磷酸化蛋白表达逐渐增高,表明重组RTB蛋白具有促进巨噬细胞活化及活化NF-κB信号通路的功能。     

牛膝多糖对仔猪肠上皮细胞免疫应激的调控及其作用机制

本试验旨在考察牛膝多糖(ABPS)对脂多糖(LPS)免疫应激下仔猪空肠上皮细胞(IPEC-J2)促炎细胞因子分泌和表达的影响,并探讨ABPS调控IPEC-J2免疫应激可能的作用机制。选用4~5代的IPEC-J2,培养基中分别添加0(对照)、300、600、900、1 200μg/m L ABPS和10μg/m L LPS,每组12个重复,每孔为1个重复。培养72 h后,采用酶联免疫吸附测定(ELISA)方法检测ABPS对促炎细胞因子白细胞介素1(IL-1)、白细胞介素6(IL-6)、白细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)分泌量的影响,采用实时定量PCR测定Toll样受体4(TLR4)、核转录因子κB(NF-κB)的mRNA表达量,采用Western blot法测定TLR4、NF-κB、磷酸化核转录因子κB(p-NF-κB)蛋白表达量。结果显示:与对照组相比,300、600、900和1 200μg/m L ABPS组能显著减少IL-1、IL-6、IL-8和TNF-α的分泌量(P0.05);300μg/m L ABPS组能显著减少p-NF-κB蛋白的表达量(P0.05),900和1 200μg/m L ABPS组能显著减少TLR4、NF-κB的mRNA和NF-κB蛋白的表达量(P0.05)。由此可见,ABPS通过TLR4/NF-κB信号转导途径来调控促炎细胞因子的分泌,从而缓解免疫应激,低浓度ABPS通过直接抑制NF-κB磷酸化过程来降低免疫应激,高浓度ABPS则是通过抑制TLR4 mRNA、NF-κB mRNA和NF-κB蛋白的表达量来缓解免疫应激。     

Transportation stress alters the expression of immunoregulatory cytokines in the porcine thymus

This study investigated the effects of transportation stress on blood concentrations of the main pro-inflammatory cytokines (interleukins IL-1β, IL-2 and IL-6; tumour necrosis factor-α) and anti-inflammatory cytokines (IL-4 and IL-10) and the expression of these cytokines and their receptors in the thymus. Pigs were assessed after 1, 2 and 4 h of transportation (n = 5 per group), with normal housing conditions as a control (n = 4). Serum concentrations of IL-2, IL-6 and IL-10 were highest at 1 h, whereas concentrations of IL-6 and IL-10 were significantly decreased at 4 h. Expression of these three cytokines and their receptors was also significantly altered in the thymus during transportation stress. Serum IL-10 concentrations and thymus IL-10 mRNA expression were significantly correlated. The thymus may contribute towards the regulation of cytokines in pigs during transportation.     

Microsphere immunoassay for the detection of cytokines in domestic cat (Felis catus) plasma: elevated IL-12/23 in acute feline immunodeficiency virus infections

We recently described the development and validation of a highly sensitive and specific microsphere immunoassay capable of simultaneously quantifying three domestic cat cytokines in tissue culture supernatant. Here we describe the modification of this assay to measure interferon gamma (IFNγ), interleukin (IL)-10 and IL-12/IL-23 p40 (IL-12/23) in domestic cat plasma, report values obtained from plasma collected after feline immunodeficiency virus (FIV) exposure, and compare plasma concentrations to blood cell mRNA expression. The validated quantitation limits of this assay are 31–1000 pg/ml for IFNγ, 63–2000 pg/ml for IL-10, and 20–625 pg/ml for IL-12/23. Plasma cytokine levels from domestic cats infected with pathogenic and/or apathogenic FIV were determined at 3–4 and 7–8 weeks post-infection. IL-12/23 was elevated (p < 0.05) during acute infection with both FIV strains in two similar studies, conducted five years apart in different feline cohorts (n = 44 total animals). IL-12/23 concentrations ranged from 377 to 1904 pg/ml in naïve cats and 552 to 3460 pg/ml in infected cats. In contrast, the majority of plasma samples had IFNγ and IL-10 concentrations below the lowest standard tested. The inability to consistently detect levels of IFNγ and IL-10 in plasma, despite the fact that mRNA changes were detected, suggests that these cytokines may be secreted and/or cleared in a more highly regulated manner than IL-12/23, or perhaps exert local effects under tighter peripheral constraints and/or at a lower effective concentration.     

基于RAGE-TLR4串扰的高糖影响牛肺泡巨噬细胞促炎细胞因子释放的分子机制

本试验旨在研究高浓度葡萄糖对牛肺泡巨噬细胞（BAMs）促炎细胞因子IL-1β、IL-6及TNF-α释放的影响及其机制是否与RAGE-TLR4相关信号通路串扰有关。将BAMs随机分为正常糖组（NG）、高糖组（HG）、高糖+RAGE抑制剂组（H+F）、高糖+TLR4抑制剂组（H+T）及DMSO组,处理12 h后收集上清及下层细胞。采用qRT-PCR和Western blot检测细胞RAGE、TLR4、MyD88、NF-κB p65的mRNA及蛋白表达情况,ELISA检测上清TNF-α、IL-1β、IL-6浓度。结果表明,高糖极显著上调RAGE、TLR4、MyD88和NF-κB p65基因、蛋白表达水平以及上清液中IL-1β、IL-6、TNF-α浓度（P<0.01）;RAGE抑制剂与TLR4抑制剂均极显著抑制高糖引起的RAGE、TLR4、MyD88和NF-κB p65基因、蛋白表达水平上调以及IL-1β、IL-6、TNF-α释放（P<0.01）,即RAGE与TLR4均在激活RAGE/TLR4/MyD88/NF-κB炎症信号通路中发挥调控作用。综上所述,高糖能够通过RAGE-TLR4串扰引起牛肺泡巨噬细胞释放促炎细胞因子IL-1β、IL-6及TNF-α,进一步阐明了高糖促进牛肺泡巨噬细胞炎症反应的分子机制。     

Organic barn dust extract exposure impairs porcine macrophage function in vitro: Implications for respiratory health

Respiratory diseases are responsible for a significant amount of animal morbidity and mortality in the swine industry, including the majority of nursery and grower/finisher deaths. Innate immunity, including the maintenance of lung macrophage health and function, is an important defense mechanism against respiratory pathogens and their associated losses. Chronic exposure of swine industry workers to airborne barn dust results in significant predisposition to airway diseases and impairment of alveolar macrophage (AM?) function. Because of their importance in maintaining normal respiratory function, this study was designed to evaluate the impact of barn dust on swine macrophages. As measures of macrophage function, we evaluated the activation of NF-κB, cytokine production, cell surface marker expression and the phagocytic and antibacterial capabilities of porcine macrophages after in vitro exposure to an organic swine barn dust extract (ODE). ODE treatment induced AM? secretion of both pro- and anti-inflammatory cytokines, suggesting a complex activation profile. Additionally, ODE induced expression of genes (TLR2, NOD2) involved in sensing Gram-positive bacteria, a major component of barn dust. ODE exposure also enhanced the expression of several cell surface markers of activation, including a receptor for the porcine reproductive and respiratory syndrome virus. Moreover, two key functions of AM?, phagocytosis and bacterial killing, were impaired after exposure to ODE. Treatment with ODE for the first 72 h of differentiation also inhibited the ability of monocyte-derived macrophages to translocate NF-κB to the nucleus following endotoxin stimulation. Taken together, these results demonstrate, for the first time, that organic dust extract exposure negatively affects pig macrophage activation and function, potentially enhancing host susceptibility to a variety of respiratory infections.     

Immunopathogenesis of porcine reproductive and respiratory syndrome in the respiratory tract of pigs

Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) impairs local pulmonary immune responses by damaging the mucociliary transport system, impairing the function of porcine alveolar macrophages and inducing apoptosis of immune cells. An imbalance between pro- and anti-inflammatory cytokines, including tumour necrosis factor-α and interleukin-10, in PRRS may impair the immune response of the lung. Pulmonary macrophage subpopulations have a range of susceptibilities to different PRRSV strains and different capacities to express cytokines. Infection with PRRSV decreases the bactericidal activity of macrophages, which increases susceptibility to secondary bacterial infections. PRRSV infection is associated with an increase in concentrations of haptoglobin, which may interact with the virus receptor (CD163) and induce the synthesis of anti-inflammatory mediators. The balance between pro- and anti-inflammatory cytokines modulates the expression of CD163, which may affect the pathogenicity and replication of the virus in different tissues. With the emergence of highly pathogenic PRRSV, there is a need for more information on the immunopathogenesis of different strains of PRRS, particularly to develop more effective vaccines.     

硒对树突状细胞和巨噬细胞功能的调控作用

旨在探讨硒对树突状细胞（dendritic cells,DCs）和巨噬细胞功能的影响,试验将硒分别与髓源性树突状细胞（bone marrow derived dendritic cells,BMDCs）和腹腔巨噬细胞共同培养后,用流式细胞术检测未成熟BMDCs和巨噬细胞的吞噬活性以及BMDCs上的MHCⅡ、CD86、CD80和CD40的表达量,测定经硒处理后的成熟BMDCs对刺激同种异体淋巴细胞增殖和抗原递呈能力,并用ELISA检测BMDCs和巨噬细胞上清液中细胞因子（IL-12、IL-1β、IFN-γ、IL-6、IL-10、TNF-α、NO）水平的变化。结果显示,当硒的质量浓度在0.18~0.09 mg·L^-1时,BMDCs和巨噬细胞的吞噬活性显著增强（P<0.05）,并且BMDCs上的MHCⅡ、CD86和CD80的表达量显著升高（P<0.05）,对刺激同种异体淋巴细胞的增殖和抗原递呈能力也显著增强（P<0.05）。此外,在BMDCs的上清中,IFN-γ、IL-12和IL-10的含量显著升高（P<0.05）;在巨噬细胞的上清中,IFN-γ、TNF-α和NO的含量显著升高（P<0.05）。结果表明,一定质量浓度的硒可以增强树突状细胞和腹腔巨噬细胞的功能,值得进一步探究硒对免疫功能的影响。     

Effects of inoculum size on cell-mediated and humoral immune responses of foals experimentally infected with Rhodococcus equi: A pilot study

The objective of this pilot study was to compare the cytokine profile as well as cell-mediated and antibody responses of foals infected with a low inoculum of virulent Rhodococcus equi resulting in subclinical pneumonia to that of foals infected with a high inoculum resulting in severe clinical pneumonia. The mean (±SD) ratio of post-infection to pre-infection anti-R. equi IgG(T) concentration was significantly (P = 0.002) higher in foals infected with the high inoculum (195 ± 145; range 62–328) compared to foals infected with the low inoculum (3.9 ± 4.5; range 0.5–11). Similarly, mean (±SD) ratio of post-infection to pre-infection IgM concentration was significantly (P = 0.002) higher in foals infected with the high inoculum (12 ± 4.0; range 7.4–14) compared to foals infected with the low inoculum (2.5 ± 1.5; range 1.2–4.7). Proliferative responses to R. equi antigens as well as expression of mRNA for IL-2, IL-4, IL-10, and IFN-γ in BLN were not significantly different between the two groups. There was a tendency (P = 0.073) towards a higher IFN-γ/IL-4 ratio in the low inoculum group. This study demonstrates that the size of inoculum modulates the IgG subisotype response and possibly the cytokine profile of foals.