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BCG and Other Vaccines
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Due to the intracellular nature of mycobacteria, cell-mediated immunity is central to protection against M.tb and control of infection. Mice deficient in CD4+ T-cells or major histocompatibility complex class II are unable to control bacterial growth and rapidly succumb to disease.106,107 Depletion of CD4+ T-cells causes reactivation of latent infection in mice,107 and increased pathology and bacterial burden during the first 8 weeks of infection in non-human primates (NHPs).108 The increased risk of TB disease due to decreased CD4+ T-cell number and function associated with HIV provides further evidence of a critical role for this cell type.109 CD8+ T-cells contribute to protective immunity through secretion of pro-inflammatory cytokines such as IFN-γ or by direct killing of M.tb-infected cells via granule-mediated functions.110M.tb lipid antigens can also be presented to unconventional T-cells such as γδ T-cells, natural killer T cells, and mucosal-associated invariant T cells, stimulating effector functions that may be of importance.111
New insights into the metabolism of Th17 cells
Published in Immunological Medicine, 2023
IL-17 is a key cytokine for host protection against mucosal and skin infection, as well as one of the major pathogenic cytokines [1–3]. The IL-17 family includes six cytokines (IL-17A to IL-17F), and five receptors (IL-17RA to IL-17RE). Besides T helper 17 (Th17) cells, TCRα+CD4−CD8− (double negative) T cells, CD8 T cells, γδ T cells, innate lymphoid cells, natural killer (NK) cells, invariant NK T cells, mucosal-associated invariant T cells, mast cells, Paneth cells and senescent T cells also produce IL-17 [3,4]. IL-1 and IL-23 are requisite for stimulating pathogenic Th17 cell differentiation and proliferation [5]. Therapeutics targeting the IL-17/IL-23 pathway are widely used in the real world or in clinical trials. Drugs targeting IL-17A (secukinumab and ixekizumab), IL-17A and IL-17F (bimekizumab), IL-17RA (brodalumab), IL-23 (guselkumab, tildrakizumab and risankizumab) and IL-12/23p40 (ustekinumab) have been shown to be effective for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis and other autoimmune diseases (Table 1) [3]. Several clinical trials involving IL-17 targeted therapy in rheumatoid arthritis or other autoimmune diseases have failed (Table 2). However, pathogenic Th17 produces not only IL-17 but also granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor α (TNFα), interferon γ (IFNγ), IL-21 and IL-22 (Table 3) [3,11,12]. Therefore, the effects of Th17-targeted therapy could be different from those of anti-IL-17 antibodies.
Role of the IL-23 pathway in the pathogenesis and treatment of enthesitis in psoriatic arthritis
Published in Expert Opinion on Biological Therapy, 2020
Maurizio Rossini, Oscar Massimiliano Epis, Ilaria Tinazzi, Rosa Daniela Grembiale, Annamaria Iagnocco
However, contrasting results have been reported concerning serum IL-23 levels in patients with inflammatory bowel diseases (IBDs) compared with SpA [81,82]. In addition to that of Th lymphocytes, IL-23, released in the gut, may induce the local activation of innate immune cells including mucosal-associated invariant T cells, γδ T cells, and innate lymphoid cells of group 3 (ILC3) [68]. Once activated, these cells may circulate in the bloodstream to the entheses, where they could give rise to inflammation. DNA from intestinal bacteria, such as Prevotella spp., can be detected in the joints and other tissues of HLA-B27-trangenic rats developing arthritis [83]. The most plausible hypothesis is that molecular fragments of intestinal microorganisms are transported into articular and periarticular sites inside circulating phagocytic cells [84]. Thus, in genetically predisposed patients, gut dysbiosis may represent the primum movens of SpA, guiding the differentiation of autoreactive clones able to migrate to articular sites.
The impact and toxicity of glyphosate and glyphosate-based herbicides on health and immunity
Published in Journal of Immunotoxicology, 2020
Cindy Peillex, Martin Pelletier
Recent studies suggest that glyphosate and GBHs interact with microorganisms and affect their interaction with the immune system. Mendler et al. (2020) studied the relationship between mucosal-associated invariant T-cells (MAIT) and gut bacteria Escherichia coli and Lactobacillus reuteri, which respectively induce and inhibit MAIT TNF and IFNγ production to control gut microbiota tolerance. Using a model with bacteria pretreated with glyphosate and subsequently cultured with MAIT, the authors showed that treated E. coli still induced the same MAIT TNF and IFNγ responses whereas treated L. reuteris increased MAIT production of TNF but not IFNγ. Hence, in this model, glyphosate reduced microbiota tolerance. A case report study described a Clostridium tertium infection after GBH ingestion for suicidal purposes in a 44-year-old woman (You et al. 2015). The authors suspected that the intestinal mucosa deterioration seen in this woman was caused by the herbicide that had allowed the bacterial infection to evolve. In conclusion, glyphosate seems to be able to disrupt interactions between bacteria and the immune system, at least at the gut interface. These changes might lead to lower microbiota tolerance or even infection development.