Excretory/secretory proteins inhibit host immune responses by downregulating the TLR4/NF-κB/MAPKs signaling pathway: A possible mechanism of immune evasion in parasitic nematode Haemonchus contortus

Wen, Zhaohai; Zhang, Yue; Feng, Jiajun; Aimulajiang, Kalibixiati; Aleem, Muhammad Tahir; Lu, Mingmin; Xu, Lixin; Song, Xiaoling; Li, Xiangrui; Ren, Yan

doi:10.3389/fimmu.2022.1013159

Cited by 8 publications

(3 citation statements)

References 85 publications

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“…In the near future, controlling some parasites with current anthelminthic medications like oxfendazole, levamisole, and ivermectin may become more challenging ( 10 ). H. contortus has evolved different strategies to evade host immune response during infection ( 12 , 13 ). Parasitic nematodes cause a long-term infection in the host, generally with just a modest inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology and phylogeny of Haemonchus contortus through internal transcribed spacer 2 gene in small ruminants

Ahmad,

Khan,

Majid

et al. 2024

Front. Vet. Sci.

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IntroductionHaemonchus contortus (H. contortus) is a blood-feeding nematode causing infectious disease haemonchosis in small ruminants of tropical and subtropical regions around the world. This study aimed to explore the prevalence and phylogeny of H. contortus in small ruminants using the internal transcribed spacer-2 (ITS-2) gene. In addition, a comprehensive review of the available literature on the status of H. contortus in Pakistan was conducted.MethodsFecal samples were collected from sheep and goats (n = 180). Microscopically positive samples were subjected to DNA extraction followed by PCR using species-specific primers.ResultsThe overall prevalence of H. contortus was 25.55% in small ruminants. The prevalence of H. contortus was significantly associated with months and area. The highest occurrence of haemonchosis was documented in July (38.70%), whereas the lowest occurred in December (11.11%), with significant difference. The prevalence was highest in the Ghamkol camp (29.4%) and lowest in the arid zone of the Small Ruminant Research Institute (17.5%) (p = 0.01). The results of the systematic review revealed the highest prevalence of haemonchosis (34.4%) in Khyber Pakhtunkhwa (p = 0.001).DiscussionPhylogenetic analysis revealed a close relationship between H. contortus and isolates from Asia (China, India, Iran, Bangladesh, Malaysia, and Mongolia) and European countries (Italy and the United Kingdom). It has been concluded that H. contortus is prevalent in small ruminants of Kohat district and all over Pakistan, which could be a potential threat to food-producing animals, farmers, dairy, and the meat industry. Phylogenetic analysis indicates that H. contortus isolates share close phylogenetic relationships with species from Asia and Europe.

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Section: Introductionmentioning

confidence: 99%

Epidemiology and phylogeny of Haemonchus contortus through internal transcribed spacer 2 gene in small ruminants

Ahmad,

Khan,

Majid

et al. 2024

Front. Vet. Sci.

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“…The TLR4/NF-κB pathway is a key signaling pathway in the immune system for detecting and responding to infection, inflammation, and external stimuli ( 13 ). This pathway involves multiple molecules and cytokines, including the TLR4 receptor, cascade-activated proteins in the pathway, and ultimately nuclear factor-κB (NF-κB), which is critical for the regulation of inflammation and immune responses ( 14 ). Senescence is a major risk factor for osteoporosis development ( 15 ), which can affect the gut microbial composition, cellular autophagy, and iron metabolism.…”

Section: Introductionmentioning

confidence: 99%

The critical role of toll-like receptor 4 in bone remodeling of osteoporosis: from inflammation recognition to immunity

Zhu,

Du,

Zhang

et al. 2024

Front. Immunol.

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Osteoporosis is a common chronic metabolic bone disorder. Recently, increasing numbers of studies have demonstrated that Toll-like receptor 4 (TLR4, a receptor located on the surface of osteoclasts and osteoblasts) plays a pivotal role in the development of osteoporosis. Herein, we performed a comprehensive review to summarize the findings from the relevant studies within this topic. Clinical data showed that TLR4 polymorphisms and aberrant TLR4 expression have been associated with the clinical significance of osteoporosis. Mechanistically, dysregulation of osteoblasts and osteoclasts induced by abnormal expression of TLR4 is the main molecular mechanism underlying the pathological processes of osteoporosis, which may be associated with the interactions between TLR4 and NF-κB pathway, proinflammatory effects, ncRNAs, and RUNX2. In vivo and in vitro studies demonstrate that many promising substances or agents (i.e., methionine, dioscin, miR-1906 mimic, artesunate, AEG-1 deletion, patchouli alcohol, and Bacteroides vulgatus) have been able to improve bone metabolism (i.e., inhibits bone resorption and promotes bone formation), which may partially attribute to the inhibition of TLR4 expression. The present review highlights the important role of TLR4 in the clinical significance and the pathogenesis of osteoporosis from the aspects of inflammation and immunity. Future therapeutic strategies targeting TLR4 may provide a new insight for osteoporosis treatment.

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“…These receptors promote a series of immune responses, including the infiltration of inflammatory cells, the activation of NK cells, and the production of antibodies, thereby enhancing the host's defense capabilities against worm invasion and parasitism [10]. Current research on the interaction between H. contortus and host pattern recognition receptors is still in its infancy, with only a few studies involving CLRs, NLRs, and TLRs [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptomic Profiling Unveils Dynamic Immune Cell Responses during Haemonchus contortus Infection

Wang,

Jin,

Kong

et al. 2024

Cells

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Background: Haemonchus contortus is a parasite widely distributed in tropical, subtropical, and warm temperate regions, causing significant economic losses in the livestock industry worldwide. However, little is known about the genetics of H. contortus resistance in livestock. In this study, we monitor the dynamic immune cell responses in diverse peripheral blood mononuclear cells (PBMCs) during H. contortus infection in goats through single-cell RNA sequencing (scRNA-Seq) analysis. Methods and Results: A total of four Boer goats, two goats with oral infection with the L3 larvae of H. contortus and two healthy goats as controls, were used in the animal test. The infection model in goats was established and validated by the fecal egg count (FEC) test and qPCR analysis of the gene expression of IL-5 and IL-6. Using scRNA-Seq, we identified seven cell types, including T cells, monocytes, natural killer cells, B cells, and dendritic cells with distinct gene expression signatures. After identifying cell subpopulations of differentially expressed genes (DEGs) in the case and control groups, we observed the upregulation of multiple inflammation-associated genes, including NFKBIA and NFKBID. Kyoto Encyclopedia of the Genome (KEGG) enrichment analysis revealed significant enrichment of NOD-like receptor pathways and Th1/Th2 cell differentiation signaling pathways in CD4 T cells DEGs. Furthermore, the analysis of ligand–receptor interaction networks showed a more active state of cellular communication in the PBMCs from the case group, and the inflammatory response associated MIF–(CD74 + CXCR4) ligand receptor complex was significantly more activated in the case group, suggesting a potential inflammatory response. Conclusions: Our study preliminarily revealed transcriptomic profiling characterizing the cell type specific mechanisms in host PBMCs at the single-cell level during H. contortus infection.

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Excretory/secretory proteins inhibit host immune responses by downregulating the TLR4/NF-κB/MAPKs signaling pathway: A possible mechanism of immune evasion in parasitic nematode Haemonchus contortus

Cited by 8 publications

References 85 publications

Epidemiology and phylogeny of Haemonchus contortus through internal transcribed spacer 2 gene in small ruminants

Epidemiology and phylogeny of Haemonchus contortus through internal transcribed spacer 2 gene in small ruminants

The critical role of toll-like receptor 4 in bone remodeling of osteoporosis: from inflammation recognition to immunity

Single-Cell Transcriptomic Profiling Unveils Dynamic Immune Cell Responses during Haemonchus contortus Infection

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