The involvement of the macrophage mannose receptor in the innate immune response to infection with parasite Trichinella spiralis

The macrophage mannose receptor (MR) is a pattern recognition receptor of the innate immune system that binds to microbial structures bearing mannose, fucose and N-acetylglucosamine on their surface. The MR can mediate endocytosis and phagocytosis, as well as activation of macrophages and antigen presentation. Since Trichinella spiralis antigens are rich in oligomannose residues, we investigated whether a mannose-recognizing receptor, such as the MR, participated in the host-parasite interaction. The results show that the MR (either on the surface of macrophages or in the purified form) recognizes and binds components of T. spiralis muscle larvae. The presence of parasites provoked activation of peritoneal macrophages, which was indicated by down-regulation of MR expression, and the stimulation of NO secretion. In vitro stimulation of macrophages with T. spiralis components resulted in increased NO and IL-6 production. However, while the MR was partially involved in stimulation of NO production, it did not mediate IL-6 secretion.     

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 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.     

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.     

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.     

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.     

Orf virus immuno-modulation and the host immune response

Orf virus encodes a range of immuno-modulatory genes that interfere with host anti-virus immune and inflammatory effector mechanisms. The function of these reflects the pathogenesis of orf. The orf virus interferon resistance protein (OVIFNR) and virus IL-10 (vIL-10) inhibit interferon production and activity. In addition the vIL-10 suppresses inflammatory cytokine production by activated macrophages and keratinocytes. The virus GM-CSF inhibitory factor (GIF) is a novel virus protein that binds to and inhibits the biological activity of GM-CSF and IL-2. Together, these immuno-modulators target key effector mechanisms of host anti-virus immunity to allow time for virus replication in epidermal cells.     

含CpG序列PRRSV ORF5基因真核表达质粒在小鼠的细胞免疫应答

为了提高猪繁殖与呼吸综合征病毒(PRRSV)基因免疫的效果,构建含CpG基序和PRRSV ORF5的真核重组表达质粒CpG-pVAX1-ORF5.经酶切鉴定和序列测定,将重组质粒转染COS-7细胞,经间接免疫荧光试验证实CpG-pVAX1-ORF5可表达PRRSV GP5蛋白.免疫SPF小鼠,检测鼠的脾T淋巴细胞亚群数量(CD4+和CD8+)以及淋巴细胞增殖反应(MTT法)水平.结果表明本试验构建的含CpG基序真核重组表达质粒CpG-pVAX1-ORF5能诱导小鼠产生针对PRRSV的细胞免疫.     

Cell-mediated immune response to rabies virus in dogs following vaccination and challenge

Peripheral blood lymphocytes (PBL) from non-vaccinated dogs and from dogs either vaccinated intramuscularly (IM) or subcutaneously (SC) with an inactivated rabies virus vaccine (Rabguard-TC, Norden Laboratories, Lincoln, NE) or intramuscularly with an attenuated rabies virus vaccine (Endurall-R, Norden Laboratories, Lincoln, NE) were exposed in vitro to rabies virus. Blastogenesis of PBL was measured by incorporation of 3H-thymidine into the DNA of proliferating cells in the presence of a suboptimal concentration of phytohemagglutinin (PHA). Following the first vaccination, there was no difference in the blastogenic response of lymphocytes from dogs vaccinated IM with either the inactivated or attenuated rabies virus vaccines. The inactivated rabies vaccine stimulated as great or greater blastogenic response when it was given SC. The PBL from non-vaccinated control dogs were not stimulated by rabies virus. Dogs vaccinated with the inactivated vaccine developed a lymphocyte blastogenic response to rabies virus following challenge with virulent street rabies virus. Nonvaccinated control dogs did not develop a lymphocyte blastogenic response to rabies virus following challenge with virulent street rabies virus.     

表达PRRSV E基因重组质粒在小鼠诱导的体液免疫应答

利用 PCR技术对猪繁殖与呼吸综合征病毒 (PRRSV) BJ- 4株的 E基因进行修饰和改造 ,在 E基因上游加入 Kozak序列 ,扩增并克隆 E基因。将 E基因 c DNA亚克隆至真核表达载体 pc DNA3.1( )中 ,构建了真核重组表达质粒 pc DNA- E。用pc DNA- E免疫小鼠 ,经免疫荧光抗体试验检测结果表明 ,重组质粒 pc DNA- E经 3次免疫后 ,所有小鼠血清抗体均为阳性 ,说明pc DNA- E在小鼠体内可诱导特异性的体液免疫应答反应。     

Humoral immune response of the bovine fetus to in utero vaccination with attenuated bovine coronavirus

A fetal response to in utero vaccination with attenuated bovine coronavirus (9 to 49 days before parturition) was determined in 8 calves, 5 vaccinated and 3 controls. Calves were derived by hysterotomy before parturition and were maintained in a closed gnotobiotic environment. The IgA, IgM, and IgG values and coronavirus-neutralizing antibody titers were higher in the sera and intestinal loop fluid from vaccinated calves than in those from control calves. Sections of ileum and ileal lymph nodes from 1-day-old vaccinated calves, when stained with monospecific anti-bovine IgG, IgM, and IgA had numerous positively stained plasma cells. Positive fluorescence was not detected in comparable tissues from controls. When the 8 calves were given virulent coronavirus orally at 6 days of age, vaccinated calves did not become ill, whereas control calves had diarrhea in 19 to 22 hours. All calves were killed at 10 days of age. Control calves had lesions characteristic of coronavirus infection, and intestinal epithelial cells were positive by fluorescent antibody tests. In vaccinated calves, lesions of coronavirus infection were absent, and results of fluorescent antibody tests were negative. Although in utero vaccination with a coronavirus vaccine stimulated immunity in the newborn calf, the frequency of abortions (2 of 14 cows inoculated intra-amniotically) and premature births (4 of 14) precluded practical application.     

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.     

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.     

Effect of passively-acquired antibodies and vaccination on the immune response to contagious ecthyma virus

Lambs which received colostrum from ewes vaccinated with contagious ecthyma (CE) virus and other lambs vaccinated with CE virus were compared for serum anti-CE immunoglobulin (Ig)G levels, delayed-type hypersensitivity (DTH) responses to CE viral antigen, and protective immunity to challenge with CE virus. Ewes vaccinated 3-4 weeks prior to parturition transferred CE antibody to lambs via colostrum. Although these lambs had higher levels of antibody at challenge than lambs vaccinated when 1-4 days old, only the vaccinated lambs were protected against challenge with CE virus at 1 month of age. Furthermore, the presence of colostrum-derived maternal antibody prevented an active antibody response in lambs to vaccination and/or challenge with CE virus, except where pre-inoculation titres were low. In contrast, the DTH response to CE viral antigen and induction of protective immunity by CE vaccination were not impaired by passively-acquired antibody. Actively immunised lambs could be distinguished from those only receiving passively-acquired antibody by the DTH response to heat-killed CE viral antigen.     

The effect of dietary lysine deficiency on the immune response to Newcastle disease vaccination in chickens

The effect of lysine deficiency on chicken immune function was evaluated using broiler chickens fed a diet with lysine at 67% of the control diet (1.24% lysine). The evaluation of humoral immune function was conducted by measuring the antibody production to a live Newcastle disease virus (NDV) vaccination using the hemagglutination inhibition (HI) test and enzyme-linked immunosorbent assay (ELISA). The cellular immune function was evaluated through the use of cutaneous basophil hypersensitivity test. The antibody response to NDV vaccination was reduced in broiler chickens fed a lysine-deficient diet when measured by ELISA but not when measured by HI. The cell-mediated immune response was also reduced by lysine deficiency.     

Cellular and humoral immune response of foals to vaccination with Corynebacterium equi.

Transformation of peripheral blood lymphocytes from pony foals vaccinated and subsequently infected with Corynebacterium equi was studied. Three foals were vaccinated on two occasions using a formalinized C. equi vaccine with aluminum hydroxide as an adjuvant. Three nonvaccinated foals served as controls. Foals were challenged intratracheally with 9 x 10(9) C. equi six weeks after the initial vaccination.Foals survived this infection for one to two weeks. Significant lymphocyte transformation in response to C. equi antigens was detected in two vaccinated foals at the third week after initial vaccination and in all vaccinated animals at the fifth week. No statistically significant transformation was seen in nonvaccinated foals before infection. Vaccinated and nonvaccinated foals showed responsive lymphocytes following challenge. Vaccination offered no obvious protection against experimental challenge but this failure was probably due to an excessive infective dose of organisms. Low levels of humoral antibodies were detected in some challenged foals. The pathological changes in the lungs of infected animals were comparable with, but more fulminating than, changes observed in the natural disease.