It is reported that different Fcγ receptors on neutrophils possess different phagocytosis capabilities, and CD32 (FcγRIIA) is the most MAPK Inhibitor Library ic50 efficient receptor among them (Rivas-Fuentes et al., 2010). The affinity of human CD32 increases during neutrophil activation leading to CD32-dependent ligand binding and signaling (Nagarajan et al., 2000). It has been documented that BCG has the capacity to increase the expression of CD32 (Suttmann et al., 2003). Similarly, in this study,
expression of CD32 was increased in BCG- and H37Rv-infected neutrophils indicating activation followed by functional upregulation of neutrophils. Another important FCγ receptor CD64 (FcγRI) that induces high respiratory burst (Hoffmeyer et al., 1997) was also upregulated in H37Rv-infected neutrophils, which further indicates a physiological response to infection (Allen et al., 2002). Neutrophils recognize pathogens via TLRs and activate various pathways
that contribute to the repertoire of defense mechanisms utilized by the immune system. Among TLRs, TLR2 is important in MTB infection and has been extensively studied. Another receptor TLR4, although important in innate immunity, Roxadustat datasheet has no direct role in protective immunity in mycobacterial infections (Reiling et al., 2002). However, it mediates the signals responsible for the production of MTB-induced IL-17A response, which strongly relies on the endogenous IL-1 pathway (van de Veerdonk Mirabegron et al., 2010). In another study, it was demonstrated that after Mtb infection neither TLR2,
-4 and -9, nor MyD88 is required for the induction of adaptive T cell responses. Rather, MyD88, but not TLR2, -4 and -9, is critical for triggering macrophage effector mechanisms central to antimycobacterial defense (Hölscher et al., 2008). In this study, an increased TLR4 expression was observed in H37Rv-stimulated neutrophils, which reflects the fact that TLR4 mediated activation of neutrophils occur during MTB infections; however, the activation does not necessarily lead to protective immune response. Neutrophils are traditionally known to express limited number of chemokine receptors; however, under inflammatory conditions, they undergo phenotypic changes, enabling them to expand their chemokine receptor expression pattern and respond to chemokines that are functionally inactive under resting conditions. The chemokine receptor CXCR3 that is normally inactive on neutrophils gets expressed when induced with TLR ligands (Hartl et al., 2008). Here, the increased expression of CXCR3 on H37Rv-infected neutrophils indicates that H37Rv has the capacity to induce the expression of CXCR3, whereas BCG and Mw are not effective enough to stimulate its expression. Neutrophils undergo spontaneous apoptosis that make them susceptible to engulfment by monocytes/macrophages.