Atherosclerosis (AS), a potentially fatal cardiovascular disease (CVD), is a chronic inflammatory condition. The disease\'s onset and progression are influenced by inflammatory and immunological mechanisms. The innate immune pathways are essential in the progression of AS, as they are responsible for detecting first danger signals and causing long-term changes in immune cells. The innate immune system possesses distinct receptors known as pattern recognition receptors (PRRs) which can identify both pathogen-associated molecular patterns and danger-associated molecular signals. Activation of PRRs initiates the inflammatory response in various physiological systems, such as the cardiovascular system. This review specifically examines the contribution of the innate immune response and PRRs to the formation and advancement of AS. Studying the role of these particular receptors in AS would enhance our understanding of the development of AS and offer novel approaches for directly improving the inflammatory response associated with it.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced non-small cell lung cancer (NSCLC), although patient survival is still unsatisfactory. Accurate predictive markers capable of personalizing the treatment of patients with NSCLC are still lacking. Circulating extracellular vesicles involved in cell-to-cell communications through miRNAs (EV-miRs) transfer are promising markers. Plasma from 245 patients with advanced NSCLC who received nivolumab as second-line therapy was collected and analyzed. EV-miRnome was profiled on 174/245 patients by microarray platform, and selected EV-miRs were validated by qPCR. A prognostic model combining EV-miR and clinical variables was built using stepwise Cox regression analysis and tested on an independent patient cohort (71/245). EV-PD-L1 gene copy number was assessed by digital PCR. For 54 patients with disease control, EV-miR changes at best response versus baseline were investigated by microarray and validated by qPCR. EV-miRNome profiling at baseline identified two EV-miRs (miR-181a-5p and miR-574-5p) that, combined with performance status, are capable of discriminating patients unlikely from those that are likely to benefit from immunotherapy (median overall survival of 4 months or higher than 9 months, respectively). EV-PD-L1 digital evaluation reported higher baseline copy number in patients at increased risk of mortality, without improving the prognostic score. Best response EV-miRNome profiling selected six deregulated EV-miRs (miR19a-3p, miR-20a-5p, miR-142-3p, miR-1260a, miR-1260b, and miR-5100) in responding patients. Their longitudinal monitoring highlighted a significant downmodulation already in the first treatment cycles, which lasted more than 6 months. Our results demonstrate that EV-miRs are promising prognostic markers for NSCLC patients treated with nivolumab.

暂无摘要。

Glaesserella parasuis is usually a benign swine commensal in the upper respiratory tract, but virulent strains can cause systemic infection characterized by pneumonia, meningitis, and fibrinous polyserositis. The intensive pulmonary inflammatory response following G. parasuis infection is the main cause of lung injury and death in pigs. Vaccination has failed to control the disease due to the lack of extended cross-protection. Accumulating evidence indicates that the heme-binding protein A (HbpA) is a potential virulence determinant and a promising antigen candidate for the development of a broader range of vaccines. However, it is not yet known whether HbpA contributes to G. parasuis virulence or has any potential immune protective effects against G. parasuis. Here, we show that HbpA can induce the transcription and secretion of proinflammatory cytokines (IL-6, TNF-α, and MCP-1) in porcine alveolar macrophages (PAM, 3D4/31). The HbpA protein is recognized by Toll-like receptors 2 and 4 on 3D4/21 macrophages, resulting in the activation of MAP kinase and NF-κB signalling cascades and the transcription and secretion of proinflammatory cytokines. HbpA contributes to virulence and bacterial pulmonary colonization in C57BL/6 mice and plays a role in adhesion to host cells and evasion of the bactericidal effect of pulmonary macrophages. In addition, mice immunized with HbpA were partially protected against challenge by G. parasuis SC1401. The results suggest that HbpA plays an important role in the pathogenesis of disease caused by G. parasuis and lay a foundation for the development of a subunit or chimeric anti-G. parasuis vaccine.

Type I interferon (IFN-I) signaling has been shown to be upregulated in systemic sclerosis (SSc). Dysregulated B-cell functions, including antigen presentation, as well as antibody and cytokine production, all of which may be affected by IFN-I signaling, play an important role in the pathogenesis of the disease. We investigated the IFN-I signature in 71 patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and 33 healthy controls (HCs). Activation via Toll-like receptors (TLRs) can influence the IFN-I signaling cascade; thus, we analyzed the effects of the TLR homologue CD180 ligation on the IFN-I signature in B cells. CD180 stimulation augmented the phosphorylation of signal transducer and activator of transcription 1 (STAT1) in dcSSc B cells (p = 0.0123). The expression of IFN-I receptor (IFNAR1) in non-switched memory B cells producing natural autoantibodies was elevated in dcSSc (p = 0.0109), which was enhanced following anti-CD180 antibody treatment (p = 0.0125). Autoantibodies to IFN-Is (IFN-alpha and omega) correlated (dcSSc p = 0.0003, HC p = 0.0192) and were present at similar levels in B cells from dcSSc and HC, suggesting their regulatory role as natural autoantibodies. It can be concluded that factors other than IFN-alpha may contribute to the elevated IFN-I signature of dcSSc B cells, and one possible candidate is B-cell activation via CD180.

Organ transplantation is characterized by a sequence of steps that involve operative trauma, organ preservation, and ischemia-reperfusion injury in the transplant recipient. During this process, the release of damage-associated molecular patterns (DAMPs) promotes the activation of innate immune cells via engagement of the toll-like receptor (TLR) system, the complement system, and coagulation cascade. Different classes of effector responses are then carried out by specialized populations of macrophages, dendritic cells, and T and B lymphocytes; these play a central role in the orchestration and regulation of the inflammatory response and modulation of the ensuing adaptive immune response to transplant allografts. Organ function and rejection of human allografts have traditionally been studied through the lens of adaptive immunity; however, an increasing body of work has provided a more comprehensive picture of the pivotal role of innate regulation of adaptive immune responses in transplant and the potential therapeutic implications. Herein we review literature that examines the repercussions of inflammatory injury to transplantable organs. We highlight novel concepts in the pathophysiology and mechanisms involved in innate control of adaptive immunity and rejection. Furthermore, we discuss existing evidence on novel therapies aimed at innate immunomodulation and how this could be harnessed in the transplant setting.

BACKGROUND: Colorectal cancer (CRC) is ranked as the third most commonly diagnosed cancer and the third cause of cancer related deaths. CRC is greatly attributed to genetic and epigenetic mutations and immune dysregulation. Tumor aberrant expression of Toll-like Receptors (TLRs) can contribute to tumorigenesis. Recent studies suggested that microRNAs act as direct ligands of TLRs altering their expression and signaling pathways.
OBJECTIVE: To prove our concept that specific miRNA mimics may act as antagonists of their specific toll like receptors inhibiting their expression that could limit the release of pro-inflammatory and pro-tumorigenic cytokines leading to apoptosis of tumor cells.
METHODS: From public microarray databases, we retrieved TLRs and miRNAs related to CRC followed by in silico docking of the selected miRNA ligands into the TLRs. Clinical validation after co-immunoprecipitation of TLRs and their interacting miRNA ligands was done. Expression of TLRs 1, 7,8 was determined by ELISA while miRNAs was measured by RT-qPCR. In addition, microRNA mimics of the down regulated miRNAs were transfected into human CRC cell lines.
RESULTS: Our data demonstrate that TLRs 1, 7, 8 are up regulated in CRC compared to controls. Further, three miRNAs (-122, -29b and -15b) are relatively downregulated, while 4 miRNAs (-202, miRNA-98, -21 and -let7i) are upregulated in CRC patients compared to those with benign tumor and healthy controls. Transfection of down regulated miRNA mimics into CRC cell lines resulted in a significant reduction of the number and viability of cells as well as down regulating the expression of TLRs 1, 7 and 8 with ultimate reduction of downstream effector IL6 protein, suggesting that these miRNAs are negative regulators of carcinogenesis.
CONCLUSIONS: MicroRNAs could act as antagonistic ligands of TLRs limiting the inflammatory tumor microenvironment.

Red blood cells (RBCs) express the nucleic acid-binding toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs express other nucleic acid-binding TLRs is unknown. Here we show that human RBCs express the RNA sensor TLR7. TLR7 is present on the red cell membrane and is associated with the RBC membrane protein Band 3. In patients with SARS-CoV2-associated sepsis, TLR7-Band 3 interactions in the RBC membrane are increased when compared with healthy controls. In vitro, RBCs bind synthetic ssRNA and RNA from ssRNA viruses. Thus, RBCs may serve as a previously unrecognized sink for exogenous RNA, expanding the repertoire of non-gas exchanging functions performed by RBCs.

Lactic acid bacteria (LAB) are commonly used in fermented foods, and some LAB modulate the immune response. We aimed to investigate the mechanism by which LAB isolates from fermented Brassica rapa L. induce the production of anti-inflammatory interleukin (IL)-10 by the murine spleen and RAW264 cells. Spleen cells from BALB/c mice or the mouse macrophage cell line RAW264 were cultured with heat-killed LAB isolated from fermented B. rapa L., and the IL-10 level in the supernatant was measured. Latilactobacillus curvatus K4G4 provided the most potent IL-10 induction among 13 isolates. Cell wall components of K4G4 failed to induce IL-10, while treatment of the bacteria with RNase A under a high salt concentration altered K4G4 induction of IL-10 by spleen cells. In general, a low salt concentration diminished the IL-10 induction by all strains, including K4G4. In addition, chloroquine pretreatment and knock down of toll-like receptor 7 through small interfering RNA suppressed K4G4 induction of IL-10 production by RAW264 cells. Our results suggest that single-stranded RNA from K4G4 is involved, via endosomal toll-like receptor 7, in the induction of IL-10 production by macrophages. K4G4 is a promising candidate probiotic strain that modulates the immune response by inducing IL-10 from macrophages.

OBJECTIVE: To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal mucosal injury induced by Cryptosporidium parvum infection, and to examine the effect of oxymatrine (OMT) on C. parvum infection in mice.
METHODS: Forty SPF 4-week-old BALB/c mice were randomly divided into four groups, including the control group, infection group, glycyrrhizin (GA) group and OMT group. Each mouse was orally administered with 1 × 105 C. parvum oocysts one week in the infection, GA and OMT groups following dexamethasone-induced immunosuppression to model C. parvum intestinal infections in mice. Upon successful modeling, mice in the GA group were intraperitoneally injected with GA at a daily dose of 25.9 mL/kg for successive two weeks, and animals in the OMT group were orally administered OMT at a daily dose of 50 mg/kg for successive two weeks, while mice in the control group were given normal food and water. All mice were sacrificed two weeks post-treatment, and proximal jejunal tissues were sampled. The pathological changes of mouse intestinal mucosal specimens were observed using hematoxylin-eosin (HE) staining, and the mouse intestinal villous height, intestinal crypt depth and the ratio of intestinal villous height to intestinal crypt depth were measured. The occludin and zonula occludens protein 1 (ZO1) expression was determined in mouse intestinal epithelial cells using immunohistochemistry, and the relative expression of HMGB1, TLR2, TLR4, myeloid differentiation primary response gene 88 (MyD88) and NF-κB p65 mRNA was quantified in mouse jejunal tissues using quantitative real-time PCR (qPCR) assay.
RESULTS: HE staining showed that the mouse intestinal villi were obviously atrophic, shortened, and detached, and the submucosal layer of the mouse intestine was edematous in the infection group as compared with the control group, while the mouse intestinal villi tended to be structurally intact and neatly arranged in the GA and OMT groups. There were significant differences among the four groups in terms of the mouse intestinal villous height (F = 6.207, P = 0.000 5), intestinal crypt depth (F = 6.903, P = 0.000 3) and the ratio of intestinal villous height to intestinal crypt depth (F = 37.190, P < 0.000 1). The mouse intestinal villous height was lower in the infection group than in the control group [(321.9 ± 41.1) μm vs. (399.5 ± 30.9) μm; t = 4.178, P < 0.01] and the GA group [(321.9 ± 41.1) μm vs. (383.7 ± 42.7) μm; t = 3.130, P < 0.01], and the mouse intestinal crypt depth was greater in the infection group [(185.0 ± 35.9) μm] than in the control group [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) and GA group [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05). The mouse intestinal villous height was greater in the OMT group [(375.3 ± 22.9) μm] than in the infection group (t = 3.888, P < 0.01), and there was no significant difference in mouse intestinal villous height between the OMT group and the control group (t = 1.989, P > 0.05). The mouse intestinal crypt depth was significantly lower in the OMT group [(121.5 ± 27.3) μm] than in the infection group (t = 4.133, P < 0.01), and there was no significant difference in mouse intestinal crypt depth between the OMT group and the control group (t = 0.575, P > 0.05). The ratio of the mouse intestinal villous height to intestinal crypt depth was significantly lower in the infection group (1.8 ± 0.2) than in the control group (3.1 ± 0.3) (t = 10.540, P < 0.01) and the GA group (2.7 ± 0.3) (t = 7.370, P < 0.01), and the ratio of the mouse intestinal villous height to intestinal crypt depth was significantly higher in the OMT group (3.1 ± 0.2) than in the infection group (t = 15.020, P < 0.01); however, there was no significant difference in the ratio of the mouse intestinal villous height to intestinal crypt depth between the OMT group and the control group (t = 0.404, P > 0.05). Immunohistochemical staining showed significant differences among the four groups in terms of occludin (F = 28.031, P < 0.000 1) and ZO1 expression (F = 14.122, P < 0.000 1) in mouse intestinal epithelial cells. The proportion of positive occluding expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.3 ± 4.5)% vs. (28.3 ± 0.5)%; t = 3.810, P < 0.01], and the proportions of positive occluding expression were significantly higher in mouse intestinal epithelial cells in the GA group [(30.3 ± 1.3)%] and OMT group [(25.8 ± 1.5)%] than in the infection group (t = 7.620 and 5.391, both P values < 0.01); however, there was no significant differences in the proportion of positive occluding expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 1.791 and 2.033, both P values > 0.05). The proportion of positive ZO1 expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.4 ± 1.8)% vs. (24.2 ± 2.8)%; t = 4.485, P < 0.01], and the proportions of positive ZO1 expression were significantly higher in mouse intestinal epithelial cells in the GA group [(24.1 ± 2.3)%] (t = 5.159, P < 0.01) and OMT group than in the infection group [(22.5 ± 1.9)%] (t = 4.441, P < 0.05); however, there were no significant differences in the proportion of positive ZO1 expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 0.037 and 0.742, both P values > 0.05). qPCR assay showed significant differences among the four groups in terms of HMGB1 (F = 21.980, P < 0.000 1), TLR2 (F = 20.630, P < 0.000 1), TLR4 (F = 17.000, P = 0.000 6), MyD88 (F = 8.907, P = 0.000 5) and NF-κB p65 mRNA expression in mouse jejunal tissues (F = 8.889, P = 0.000 7). The relative expression of HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] and NF-κB p65 mRNA [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] was all significantly higher in mouse jejunal tissues in the infection group than in the control group. A significant reduction was detected in the relative expression of HMGB1 (0.63 ± 0.01), TLR2 (0.42 ± 0.10), TLR4 (0.35 ± 0.07), MyD88 (0.70 ± 0.11) and NF-κB p65 mRNA (0.75 ± 0.01) in mouse jejunal tissues in the GA group relative to the control group (t = 8.629, 5.830, 11.500, 4.729 and 6.898, all P values < 0.05), and the relative expression of HMGB1, TLR2, TLR4, MyD88 and NF-κB p65 mRNA significantly reduced in mouse jejunal tissues in the GA group as compared to the infection group (t = 7.052, 6.035, 4.084, 3.165 and 3.274, all P values < 0.05). In addition, the relative expression of HMGB1 (1.14 ± 0.60), TLR2 (1.00 ± 0.24), TLR4 (1.14 ± 0.07), MyD88 (0.96 ± 0.25) and NF-κ B p65 mRNA (1.12 ± 0.17) was significantly lower in mouse jejunal tissues in the OMT group than in the infection group (t = 7.059, 5.320, 3.510, 3.466 and 3.273, all P values < 0.05); however, there were no significant differences between the OMT and control groups in terms of relative expression of HMGB1, TLR2, TLR4, MyD88 or NF-κB p65 mRNA in mouse jejunal tissues (t = 0.239, 0.518, 1.887, 0.427 and 0.641, all P values > 0.05).
CONCLUSIONS: C. parvum infection causes intestinal inflammatory responses and destruction of intestinal mucosal barrier through up-regulating of the HMGB1-TLR2/TLR4-NF-κB pathway. OMT may suppress the intestinal inflammation and repair the intestinal mucosal barrier through inhibiting the activity of the HMGB1-TLR2/TLR4-NF-κB pathway.
［摘要］ 目的 探讨高迁移率族蛋白B1 (high mobility group box protein B1, HMGB1)-Toll样受体2 (Toll-like receptor 2, TLR2)/TLR4-核因子κB (nuclear factor κB, NF-κB) 通路在微小隐孢子虫感染致肠黏膜损伤中的作用, 以及氧化苦参碱 (oxymatrine, OMT) 对小鼠微小隐孢子虫感染的干预作用。方法 4周龄SPF级BALB/c小鼠40只随机分成4组, 分别为 对照组、感染组、甘草酸 (glycyrrhizin, GA) 组及OMT组。感染组、GA组及OMT组小鼠给予地塞米松免疫抑制1周后, 每 只灌胃1 × 105个微小隐孢子虫卵囊建立微小隐孢子虫肠道感染小鼠模型。模型建立成功后, GA组小鼠连续2周腹腔注 射GA 25.9 mL/(kg·d), OMT组连续2周经口灌胃OMT 50 mg/(kg·d); 对照组正常饮食、饮水。治疗2周后剖杀各组小鼠, 取空肠近端组织。采用苏木精-伊红 (hematoxylin-eosin, HE) 染色观察小鼠肠黏膜病理变化, 测量肠绒毛高度、肠隐窝深 度及两者比值; 采用免疫组织化学染色检测小鼠肠上皮细胞中闭合蛋白 (occludin) 和紧密粘连蛋白1 (zonula occludens protein 1, ZO1) 表达水平, 采用实时荧光定量PCR (quantitative real-time PCR, qPCR) 检测小鼠空肠组织中HMGB1、TLR2、 TLR4、髓样分化因子88 (myeloid differentiation primary response gene 88, MyD88) 、NF-κB p65mRNA相对表达量。结果 HE 染色结果显示, 与对照组比较, 感染组小鼠肠绒毛明显萎缩变短、脱落, 黏膜下层水肿; GA组和OMT组小鼠肠绒毛结构 趋于完整, 排列趋于整齐。各组小鼠肠绒毛高度 (F = 6.207, P = 0.000 5) 、肠隐窝深度 (F = 6.903, P = 0.000 3) 及两者比 值 (F = 37.190, P < 0.000 1) 差异均有统计学意义。感染组小鼠肠绒毛高度 [(321.9 ± 41.1) μm] 显著低于对照组 [(399.5 ± 30.9) μm] (t = 4.178, P < 0.01) 和GA组 [(383.7 ± 42.7) μm] (t = 3.130, P < 0.01), 感染组小鼠肠隐窝深度 [(185.0 ± 35.9) μm] 显著高于对照组 [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) 及GA组 [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05) 。OMT组小 鼠肠绒毛高度 [(375.3 ± 22.9) μm] 显著高于感染组 (t = 3.888, P < 0.01), 与对照组差异无统计学意义 (t = 1.989, P > 0.05); OMT组小鼠肠隐窝深度 [(121.5 ± 27.3) μm] 显著低于感染组 [(185.0 ± 35.9) μm] (t = 4.133, P < 0.01), 与对照组差异无统 计学意义 (t = 0.575, P > 0.05) 。感染组小鼠肠绒毛高度与肠隐窝深度比值 [(1.8 ± 0.2) ] 显著低于对照组 [(3.1 ± 0.3) ] (t = 10.540, P < 0.01) 及GA组 [(2.7 ± 0.3) ] (t = 7.370, P < 0.01); OMT组小鼠肠绒毛高度与肠隐窝深度比值 [(3.1 ± 0.2) ] 显著 高于感染组 (t = 15.020, P < 0.01), 与对照组差异无统计学意义 (t = 0.404, P > 0.05) 。免疫组织化学染色结果显示, 各组 小鼠肠上皮细胞中occludin (F = 28.031, P < 0.000 1) 及ZO1表达水平差异均有统计学意义 (F = 14.122, P <0.0001) 。感染组 小鼠肠上皮细胞中occludin阳性表达率 [(14.3 ± 4.5) %] 低于对照组 [(28.3 ± 0.5) %] (t = 3.810, P < 0.01), GA组 [(30.3 ± 1.3) %] 、OMT组小鼠肠上皮细胞中occludin阳性表达率 [(25.8 ± 1.5) %] 显著高于感染组 (t = 7.620、5.391, P 均< 0.01), 但GA组、OMT组小鼠肠上皮细胞中occludin阳性表达率与对照组差异均无统计学意义 (t = 1.791、2.033, P 均> 0.05) 。 感染组小鼠肠上皮细胞中ZO1阳性表达率 [(14.4 ± 1.8) %] 显著低于对照组 [(24.2 ± 2.8) %] (t = 4.485, P < 0.01), GA组 [(24.1 ± 2.3) %] (t = 5.159, P < 0.01) 、OMT组小鼠肠上皮细胞中ZO1阳性表达率 [(22.5 ± 1.9) %] 显著高于感染组 (t = 4.441, P < 0.05), 但GA组、OMT组小鼠肠上皮细胞中ZO1阳性表达率与对照组差异均无统计学意义 (t = 0.037、0.742, P 均> 0.05) 。qPCR检测结果显示, 各组小鼠空肠组织中HMGB1 (F = 21.980, P < 0.000 1) 、TLR2 (F = 20.630, P < 0.000 1) 、 TLR4 (F = 17.000, P = 0.000 6) 、MyD88 (F = 8.907, P = 0.000 5) 、NF-κB p65 mRNA 表达水平差异均有统计学意义 (F = 8.889, P = 0.000 7) 。感染组小鼠空肠组织中HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] 、NF-κB p65 mRNA 相对表达量 [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] 均 显著高于对照组。与对照组比较, GA组小鼠空肠组织中HMGB1 (0.63 ± 0.01) 、TLR2 (0.42 ± 0.10) 、TLR4 (0.35 ± 0.07) 、 MyD88 (0.70 ± 0.11) 、NF-κB p65 mRNA 相对表达量 (0.75 ± 0.01) 均显著下降 (t = 8.629、5.830、11.500、4.729、6.898, P 均< 0.05) 。与感染组比较, GA组小鼠空肠组织中HMGB1、TLR2、TLR4、MyD88、NF-κB p65 mRNA 相对表达量均显著降低 (t = 7.052、6.035、4.084、3.165、3.274, P 均< 0.05); OMT 组小鼠空肠组织中HMGB1 (1.14 ± 0.60) 、TLR2 (1.00 ± 0.24) 、TLR4 (1.14 ± 0.07) 、MyD88 (0.96 ± 0.25) 、NF-κB p65 mRNA 相对表达量 (1.12 ± 0.17) 亦显著低于感染组 (t = 7.059、5.320、3.510、 3.466、3.273, P 均< 0.05) 。OMT组与对照组小鼠空肠组织中HMGB1、TLR2、TLR4、MyD88、NF-κB p65 mRNA 相对表达量 差异均无统计学意义 (t = 0.239、0.518、1.887、0.427、0.641, P均> 0.05) 。结论 微小隐孢子虫感染小鼠后通过上调 HMGB1-TLR2/TLR4-NF-κB 通路表达引起肠道炎症反应、破坏肠黏膜屏障。OMT 可能通过抑制HMGB1-TLR2/TLR4-NF-κB 通路活性抑制小鼠肠道炎症, 并修复肠黏膜屏障。.