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1.
Equine theileriosis due to Theileria equi is probably the most widespread and pathogenic disease of equines, which comes with major cardiac and renal complications. This study was undertaken to investigate the biomarkers of cardiac and renal functions in horses infected with T. equi and determine the association between these parameters and the level of parasitemia. Giemsa-stained blood smears from 300 horses with ages of 3–4 years old were examined for detection of T. equi on erythrocytes. Moreover, multiplex PCR was employed for confirmation of the diagnosis in the 28 positive cases. Based on the rate of red blood cell infection, the infected animals were subdivided into horses with low (n = 9), moderate (n = 13) and high (n = 6) parasitemia. The concentrations of urea, creatinine, cystatin-C, cardiac troponin I (cTn-I), homocysteine (Hcy), myocardial fractions of creatine kinase (CK-MB) and d-dimer were determined in control (healthy) horses (n = 20) and the infected animals. The results revealed that both the renal (urea, creatinine and cystatin-C) and the cardiac (cTn-I, Hcy, CK-MB and d-dimer) biomarkers increased in a parasitemia burden-dependent pattern. However, urea, creatinine, cTn-I and d-dimer levels were not significantly influenced in the horses infected with low rate (<1 %) of parasitemia (p> 0.05). Moreover, all of the biomarkers were significantly and positively associated with the parasitemia (R2> 0.5). In conclusion, T. equi infection was related to cardiac and renal complications evidenced by increase in the levels of biomarkers and evaluation of these indices may have promise for early diagnosis of the complications.  相似文献   

2.
The infection with protozoan parasite Theileria annulata induces changes triggering the activation and/or proliferation of the host lymphocytes. In order to find out the possible correlations among peripheral circulatory lymphocytes, cytokine activities and the level of sialic acids, 50 dairy Holstein cattle, naturally infected with T. annulata, were divided into 4 subgroups according to their parasitemia rates (<1%, 1–3%, 3–5% and >5%). Also, ten non-infected cattle were sampled as control group. Blood samples were taken from jugular vein into acid citrate dextrose-containing tubes for measuring hematological parameters and B and T (CD4 and CD8) cell populations and without anticoagulant for TNF-α, IFN-γ and sialic acid concentrations. Remarkable decreases observed in red blood cells (RBCs), white blood cells (WBCs) and packed cell volume (PCV) in infected cattle compared to healthy ones (P < 0.05). Also, with increase in parasitemia rate, total lymphocytes and monocytes alleviated in the diseased groups. By contrast, total neutrohpils and the concentrations of TNF-α, IFN-γ and total sialic acids were significantly elevated (P < 0.05) in infected animals. Accordingly, the circulatory populations of CD4 and CD8 T cells and B cells showed a substantial decrease, while a significant increase was observed in T (CD4 and CD8) cells in cattle infected with <1% parasitemia rates. Decreased circulatory T cell population shows the ineffective responses of T cells to the stimulatory cytokines such as IFN-γ or TNF-α. On the other hand, the elevation of cytokines (particularly IFN-γ) and sialic acids have presumably an inhibitory role on circulatory B cell population in infected cattle. In addition, a high level of sialic acid concentration indicates the probable role of sialic acid to regulate the parasite-host cell adhesion during sporozoites invasion.  相似文献   

3.
The aim of this study was to measure the levels of inflammatory mediators in serum from horses naturally infected with Trypanosoma vivax. Banked serum samples collected during a previously reported T. vivax natural infection were used to analyze proinflammatory cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate (NOx) levels. We evaluated 12 serum samples from horses from a farm in southern Brazil, four of which had parasitological and molecular diagnoses for T. vivax and presented with clinical signs of disease. Cytokines were assessed by quantitative sandwich enzyme-linked immunosorbent assay, and NOx was measured using the modified Griess method. Levels of IFN-γ, TNF-α, IL-1, IL-6, and NOx were increased in serum of infected animals compared to that in noninfected animals. Therefore, infection with T. vivax caused an increase in proinflammatory cytokines and nitric oxide content.  相似文献   

4.
Newcastle disease (ND) is a highly contagious avian disease and one of the major causes of economic losses in the poultry industry. The emergence of virulent NDV genotypes and repeated outbreaks of NDV in vaccinated chickens have raised the need for fundamental studies on the virus–host interactions. In this study, the profiles of B and T lymphocytes and macrophages and differential expression of 26 immune-related genes in the spleen of specific-pathogen-free (SPF) chickens, infected with either the velogenic genotype VII NDV strain IBS002 or the genotype VIII NDV strain AF2240, were evaluated. A significant reduction in T lymphocyte population and an increase in the infiltration of IgM+ B cells and KUL01+ macrophages were detected in the infected spleens at 1, 3 and 4 days post-infection (dpi) (P < 0.05). The gene expression profiles showed an up-regulation of CCLi3, CXCLi1, CXCLi2 (IL-8), IFN-γ, IL-12α, IL-18, IL-1β, IL-6, iNOS, TLR7, MHCI, IL-17F and TNFSF13B (P < 0.05). However, these two genotypes showed different cytokine expression patterns and viral load. IBS002 showed higher viral load than AF2240 in spleen at 3 and 4 dpi and caused a more rapid up-regulation of CXCLi2, IFN-γ, IL-12α, IL-18, IL-1β, iNOS and IL-10 at 3 dpi. Meanwhile, the expression levels of CCLI3, CXCLi1, IFN-γ, IL-12α, IL-1β and iNOS genes were significantly higher in AF2240 at 4 dpi. In addition, the expression levels of IL-10 were significantly higher in the IBS002-infected chickens at 3 and 4 dpi. Hence, infection with velogenic genotype VII and VIII NDV induced different viral load and production of cytokines and chemokines associated with inflammatory reactions.  相似文献   

5.
Rhodococcus equi is an intracellular pathogen of macrophages that causes rhodococcal pneumonia in foals and immunocompromised people. Evidence exists that neutrophils play a vital role in resistance to infection with R. equi; however, the means by which neutrophils exert their effects have not been clearly defined. In addition to directly killing bacteria, neutrophils also may exert a protective effect by linking innate and adaptive immune responses. In the present study we evaluated the cytokine expression profiles of adult equine neutrophils in response to stimulation with isogenic strains of virulent and avirulent R. equi in vitro. After 2 and 4 h incubation with virulent or avirulent R. equi, adult equine neutrophils expressed significantly (P < 0.05) greater tumor necrosis factor alpha (TNFα), interleukin (IL)-12p40, IL-6, IL-8 and IL-23p19 mRNA, but not interferon gamma (IFNγ) or IL-12p35 mRNA than unstimulated neutrophils. Furthermore, virulent R. equi induced significantly greater IL-23p19 mRNA than avirulent R. equi. These results demonstrate that R. equi-stimulated neutrophils are a source of many proinflammatory cytokines. Furthermore, these results suggest that IL-23 may be preferentially expressed over IL-12 in response to exposure with R. equi, and that this response may be more strongly induced by virulent R. equi than avirulent R. equi. Collectively, the data presented herein suggest a non-phagocytic role for neutrophils that may influence the type of adaptive immune response to R. equi.  相似文献   

6.
Neosporosis is a disease known to cause reproductive problems in cattle. In horses, the disease is caused by the protozoa Neospora caninum and/or Neospora hughesi, but little is known about this infection in this species. Therefore, the aim of this study was to quantify the levels of immunoglobulins (Igs), cytokines, and acute phase protein in seropositive horses for Neospora spp. (n = 23) comparing with seronegative horses (n = 20). There was no significant difference (P > .05) between IgG levels; however, IgM levels were significantly higher in sera samples from positive animals (P < .01). Similarly, proinflammatory cytokines (tumor necrosis factor, interferon gamma, interleukins [IL-1, IL-4, and IL-6]) and C-reactive protein levels were also significantly higher (P < .01) in horses seropositive for Neospora spp. On the other hand, the IL-10 levels (anti-inflammatory cytokine) were lower in horses seropositive for neosporosis (P < .01). Therefore, we conclude that horses naturally infected by Neospora spp., even without clinical disease, are able to activate their immune systems to control the infection, which may lead to disease chronicity.  相似文献   

7.
Pietra  M.  Morini  M.  Perfetti  G.  Spadari  A.  Vigo  P.  Peli  A. 《Veterinary research communications》2010,34(1):121-124

In recent years, gastric ulceration has been recognized as a common, possibly performance-limiting disease, of adult horses. The aim of this study was to compare endoscopic features, histological diagnosis, and mRNA levels of various cytokines (TNF-α, IL-1β, and IL-13) from horse gastric biopsies. Eleven horses suffering from equine gastric ulcer syndrome and seven horses with normal histological gastric features were assessed. No correlation between endoscopic features and histology (i.e., the gold standard) was observed. Based on histological diagnosis, a significant (p < 0.05) increase in cytokine mRNA levels (specifically, TNF-α and IL-13) was observed in horses affected by equine ulcerative gastric syndrome.

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8.
Theileriosis is a worldwide protozoal tick-borne disease caused by Theileria equi, which may produce a variety of clinical signs and turn infected horses into lifetime carriers. This study has aimed to perform a serological and molecular detection of T. equi and associated factors in sports horses from six areas of northeastern Brazil. In overall, 59.6% horses were positive by indirect immunofluorescence assay and 50.4% by polymerase chain reaction. No significant association was found when presence of ticks, age, gender, anemia or total plasma proteins was analyzed with seropositivity and molecular techniques. Although a significant association of infection was found in two cities. Thus, local risk factors other than presence of ticks, horse age, gender, anemia and total plasmatic proteins may dictate prevalence of T. equi infection in sports horses, even in highly endemic areas with no control of infection prior to horse competitions.  相似文献   

9.
Equine piroplasmosis (EP) is a tick-borne protozoal disease of horses, mules, donkeys, and zebras that is characterized by acute hemolytic anemia. The etiologic agents are two hemoprotozoan parasites, Theileria equi (Laveran, 1901) and Babesia caballi (Nutall and Strickland, 1910) that are transmitted primarily by ixodid ticks. Equine piroplasmosis is found globally where tick vectors are present and is endemic in tropical, subtropical, and some temperate regions. Horses infected with B. equi remain seropositive for life; horses infected with B. caballi are seropositive for several years to life. Economic losses associated with EP are significant and include the cost of treatment, especially in acutely infected horses; abortions; loss of performance; death; and restrictions in meeting international requirements related to exportation or participation in equestrian sporting events. Equine babesiosis–free countries limit the entrance of Babesia-seropositive horses into their countries. In the United States a few sporadic outbreaks have occurred in recent years but have been limited due to implementation of stringent control methods. The cELISA for both T. equi and B. caballi is currently the recommended test for international horse transport. Different therapies for control and sterilization of the parasites are discussed.  相似文献   

10.
This study is designated to assess the effect of the severity of Babesia ovis infection on sialic acid concentration in blood sera in naturally infected sheep. Infected animals (diseased group) comprised 38 Iranian fat-tailed sheep, about 1–3 years old, naturally infected with B. ovis, divided into four subgroups with respect to parasitemia rates (low 0.1–0.3 %, moderate 0.4–0.9 %, high 1–2.5 %, and very high >2.5 %). The parasitological diagnosis was confirmed using PCR analysis. As a control group, ten clinically healthy sheep reared under the same management and environmental conditions were also sampled. Hematological parameters and the concentrations of total sialic acid (TSA), lipid-bound sialic acid (LBSA), and protein-bound sialic acid (PBSA) were measured in both groups. Compared to controls, sialic acid concentrations showed significant increase (p?Parasitemia rate was positively correlated with sialic acid concentrations. This study demonstrated that B. ovis infection induced marked and persistent elevations of serum sialic acid concentrations. It seems that increase of serum sialic acid concentrations during parasitemia alter receptor-ligand interactions, which are known to play important role in immune response. Furthermore, sialic acid would indirectly inhibit the action of leukocytes and consequently promote the evasion of the immune response and persistence of the parasite in the host. This factor could influence the parasite-host cell adhesion, but further detailed biochemical investigations are needed to precisely explain the exact role of sialic acid in invasion process of the parasite to the host cells.  相似文献   

11.
In this study, to evaluate the influence of strangles vaccination on serological test results, we investigated the changes in strangles serum antibody levels in horses after vaccination and subsequent intranasal challenge with S. equi. The horses were vaccinated for strangles with either a component vaccine (Group C) or a live vaccine (Group L). We measured changes in strangles serum antibody levels weekly for 20 weeks after vaccinating horses twice for strangles over a 3-week interval, and for 7 weeks after intranasal challenge with S. equi in the same horses. Serum antibody responses to the proline-glutamic acid-proline-lysine (PEPK) antigen with five repetitions (PEPK-5R) were higher at all times (up to 2.4-fold) following vaccination in Group C than in Group L, and the value peaked at 2.9-fold above the initial value after the second vaccination in Group C horses. However, the value was lower than that in horses infected with S. equi, and it gradually decreased, reaching the initial (week 0) value by the 15th week. Serum antibody responses to PEPK-5R after challenge with S. equi increased in both groups of horses, but the value tended to be lower than that reported for unvaccinated horses. In addition, the average value in Group C was 2.6-fold higher than that of Group L. These results suggest the serum antibody responses of horses infected with S. equi varies according to the type of vaccine with which they have been vaccinated. Although the serological diagnostic test for strangles in which PEPK-5R is used as an antigen is effective for the investigation of serum antibodies to strangles in vaccinated horses, the present data suggest it is necessary to consider the vaccination history when interpreting the results.  相似文献   

12.
Toxoplasmosis is an important parasitic disease affecting several species of mammals, but little is known about this disease in horses. This study aimed to investigate the levels of several immunological variables and markers of cell damage in the serum of seropositive horses for Toxoplasma gondii. Sera samples of adult horses from the Santa Catarina State, Brazil used on a previous study were divided into groups according to their antibody levels for T. gondii determined by immunofluorescence assay, i.e. 20 samples from seronegative horses (Group A – control), 20 samples from horses with titers of 1:64 (Group B), 20 samples of horses with titers of 1:256 (Group C), and five samples from horses with titers of 1:1024 (Group D). Positive animals (Groups B, C, and D) had higher levels of immunoglobulins (IgM and IgG), pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1, IL-4, and IL-6) and protein C-reactive protein, as well as lower levels of IL-10 (anti-inflammatory cytokine) when compared to seronegative horses (Group A). The nitric oxide levels were also elevated in seropositive horses. Therefore, we have found humoral and cellular immune responses in seropositive horses, and a correlation between high antibody levels and inflammatory mediators. Markers of cell injury by lipid peroxidation (TBARS) and protein oxidation (AOPP) were elevated in animals seropositives for T. gondii when compared to seronegatives. Therefore, seropositive horses to T. gondii can keep active immune responses against the parasite. As a consequence with chronicity of disease, they show cellular lesions that may lead to tissue damage with the appearance of clinical disease.  相似文献   

13.
Strangles is one of the most frequently diagnosed equine respiratory infectious diseases in the world. It is caused by Streptococcus equi subsp. equi (S. equi), and it is an acute infection characterized by pyrexia, nasal discharge, pharyngitis, and abscessation of lymph nodes. Frequently, healthy horses might continue to harbor S. equi after clinical recovery. Although the genetic distance between S. equi isolates is short, strains can be differentiated by pulsed-field gel electrophoresis (PFGE) and single locus sequence typing for epidemiological studies. The aim of this study was to characterize by PFGE Argentine isolates of S. equi obtained from horses with acute strangles and those that had recovered. Bacterial isolation and identification of 80 S. equi isolates by phenotypic and genotypic tests were performed using samples from 29 horses with acute strangles and 95 from healthy animals. Also, the isolates were characterized by PFGE using Bsp120I and SmaI. Visual comparison of macrorestriction patterns generated with both enzymes revealed three different DNA fragment profiles with variations of one or two bands. Interestingly, an identical profile was found in isolates from the same horse and from horses that were infected at the same time, and the horses recovered from strangles continue to carry the same strain. Some vaccinated horses have been mild infected for a different strain from that of carriers suggesting other source of infection. This is the first molecular characterization of Argentine isolates of S. equi, which shows the presence of three strains between 2010 and 2013 in Buenos Aires.  相似文献   

14.
Ehrlichia equi, etiologic agent of equine ehrlichiosis, is a rickettsia which morphologically closely resembles the agents of bovine petechial fever, tick-borne fever, and canine ehrlichiosis (tropical canine pancytopenia). Natural infections of E. equi have been reported only in horses; however, the experimental host range of E. equi has been broadened to include burros, sheep, goats, dogs, cats, monkeys and baboons. Infection of primates indicates that E. equi may be a zoonotic agent. An indirect fluorescent antibody test employing E. equi-infected granulocytes as antigen has been developed and used to show that infected horses develop a prolonged antibody response to E. equi. Cell-mediated immune responses measured by the leukocyte migration inhibition test were also detected in horses recovered from acute illness. Protective immunity in horses, monkeys and baboons to reinfection is long-lasting. In contrast to the blood of dogs recovered from clinical E. canis infection, the blood of horses and dogs recovered from clinical infection with E. equi is not infectious for susceptible animals. Infection of dogs with E. equi does not provide protection against subsequent infection with E. canis.  相似文献   

15.
16.
Clostridium difficile (CD) is considered a major health care problem both in developing and developed countries; frequently reported to be associated with enterocolitis and diarrhea in horses and other animals. In this study, we examined acute phase response (APR), cytokines response, neopterin (NP) procalcitonin (PCT) production and oxidative stress condition in horses and foals with C. difficile-induced enterocolitis (CDIE) and evaluated the effectiveness of these parameters as biomarkers for the disease. A total of 407 Arabian horses in 35 stables were examined between January 2017 to December 2018. Only 24 out of 407 horses showed two or more signs of CDIE. The blood level of serum amyloid A (SAA), haptoglobin (HP), proinflammatory cytokines (TNF-α, IL-6 and IL1-β), serum malondialdehyde (MDA), PCT and NPT in horses with CDIE were higher than in healthy horses. Nevertheless, the levels of nitric oxide (NO), superoxide dismutase (SOD) and total antioxidant concentration (TAC) were considerably lower in diseased horses compared to those that were healthy. The ROC curves for eleven selected blood parameters, both in healthy horses and horses with CDIE demonstrated that all examined blood markers had significant levels of differentiation between CDIE cases and healthy controls (AUC > 87.5). The data in this study suggest that the evaluation of acute-phase proteins, cytokines, PCT, NPT, and oxidative stress biomarkers may well be used as a tool for diagnosis and assessment of CDIE and in disease pathogenesis in Arabian horses.  相似文献   

17.
A cross-sectional study was carried out on equids (horses, mules and donkeys) in Andalusia, Southern Spain, to assess the level of exposure to equine piroplasmosis and to investigate risk factors associated with these infections. At least one animal seropositive for Theileria equi and/or Babesia caballi was detected in 222/380 (58.4%) herds sampled by competitive inhibition ELISAs. The seroprevalences for B. caballi and T. equi were 13.2% and 56.1%, respectively; there was serological evidence of co-circulation of both piroplasms in 10.8% of herds. Antibodies against equine piroplasms were detected in 286/537 (53.3%) animals; 61 (11.4%) were seropositive for B. caballi, 270 (50.3%) were seropositive for T. equi and 24 (8.4%) were seropositive for both T. equi and B. caballi.There was a significantly higher seroprevalence of B. caballi in mules (32.1%) compared with donkeys (17.0%) and horses (7.9%), and a significantly higher seroprevalence of T. equi in mules (66.1%) in comparison with horses (48.6%), but not donkeys (47.2%). There were significant differences in prevalence of both piroplasms among locations; the seroprevalence of B. caballi ranged from 0 to 22.5%, while the seropositivity to T. equi ranged from 26.7 to 63.3%. A multiple logistic regression model indicated that the risk factors associated with a higher T. equi seroprevalence were increased age, presence of ticks and vaccination against other diseases. Risk factors associated with a higher seroprevalence of B. caballi were species (mules compared to horses), entry of horses in the last 6 months, presence of ticks and presence of shelter. The findings indicate widespread exposure to equine piroplasmosis in Southern Spain.  相似文献   

18.
This study was undertaken to evaluate the acute phase responses via the assessment of the concentration of serum sialic acids (total, lipid bound and protein bound), inflammatory mediators (IFN-γ and TNF-α) and acute phase proteins (Hp and SAA) in 20 adult crossbred cattle naturally infected by Anaplasma marginale. The infected animals were divided into 2 subgroups on the basis of parasitemia rate (<20% and >20%). Also, as a control group, 10 clinically healthy cattle from the same farms were sampled. Our data revealed significant decreases in red blood cell count (RBC), hematocrite (PCV) and hemoglobine (Hb) in infected cattle compared to healthy ones. Conversely, the concentrations of Hp, SAA, ceruloplasmin, fibrinogen, serum sialic acids and the circulatory IFN-γ and TNF-α were increased in the diseased cattle (P<0.05). In addition, it was evident that the progression of parasitemia in infected cattle did not induce any significant alterations in the hematological indices (RBCs, PCV and Hb) and the concentrations of Hp, SAA, ceruloplasmin and fibrinogen. SAA was the most sensitive factor to change in the diseased cattle. Therefore, increase in SAA concentration may be a good indicator of inflammatory process in cattle naturally infected with Anaplasma marginale.  相似文献   

19.
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.  相似文献   

20.
旨在探究脂肪酸氧化(fatty acid oxidation,FAO)对BCG介导的RAW264.7细胞自噬和促炎因子表达的调控作用。用BODIPY染色和游离脂肪酸定量试剂盒检测BCG感染后RAW264.7细胞中脂滴聚集情况以及脂肪酸含量;Western blot检测BCG感染对肉毒碱棕榈酰基转移酶1A (CPT-1A)表达的影响;Etomoxir (100 μmol·L-1)预处理细胞2 h后,BCG感染细胞6 h,检测RAW264.7细胞中BCG存留量,并用Western blot方法检测自噬相关蛋白(Beclin1、LC3-II)和溶酶体蛋白(Rab7)的表达情况;用免疫荧光方法和mRFP-GFP-LC3荧光双标腺病毒分别检测自噬小体聚集和自噬流;荧光定量PCR和ELISA分别检测促炎因子IL-1β、IL-6和TNF-α mRNA表达情况以及在细胞培养上清中的含量。结果显示,BCG感染促进RAW264.7细胞中脂滴聚集和CPT-1A的表达,而游离脂肪酸含量降低;Etomoxir预处理抑制了细胞中BCG存活,并上调了Beclin1、LC3-II和Rab7表达,且细胞中出现大量自噬小体聚集,自噬流增强,却抑制了促炎因子IL-1β、IL-6和TNF-α mRNA表达与分泌。综上表明,抑制FAO可促进BCG感染诱导的RAW264.7细胞自噬,并抑制BCG感染引起的炎症反应。  相似文献   

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