Posttreatment Downregulation of Type III Interferons in Patients with Acute Brucellosis

Figure 2

Interactions of Brucella spp. with the immune system. After the activation of antigen-presenting cells (APCs) with Brucella antigen via the Toll-like receptor (TLR) signaling pathway, a cascade of events leads to the priming of CD4⁺ T cells to helper T cells type 1 (Th₁) and type 2 (Th₂). Th₁ cells secrete various cytokines, such as TNF-α and IFN-γ, which activate and enhance the anti-Brucella mechanisms of macrophages and activate CD8⁺ T cells, which boost the immune responses of macrophages even further. Moreover, APCs can trigger Th₂ activation, which switches on B lymphocytes and the humoral immunity, facilitating the opsonization and faster eradication of the pathogen from the host’s body. It is noteworthy that Th₁ and Th₂ cells can inhibit either pathway via secreting cytokines, such as IFN-γ and IL-10, respectively. Furthermore, macrophages can be stimulated by secreting another cytokine called type III interferons or interferon-λ by APCs or epithelial cells. These activated macrophages exert their immunomodulatory effects through two different pathways: direct and indirect. In the direct pathway, chemokine and inflammatory cytokine expression, antigen recognition and presentation, and macrophages’ cytotoxicity are elevated. Through the indirect pathway, these cells can enhance natural killer (NK) and T cell chemotaxis and NK cell cytotoxicity and elevate the production and release rate of IFN-γ, which in turn, via activating the Th₁ pathway, helps better and faster eradication of Brucella spp. Abbreviations: TLR: Toll-like receptor; ILC: innate lymphocyte cells; IL-12: interleukin-12; APC: antigen-presenting cells; B7: cluster of differentiation 80/86; MHC II: major histocompatibility complex type 2; CD28: cluster of differentiation 28; TCR: T cell receptor; IFN-γ: interferon-gamma; TNF-α: tumor necrosis factor-alpha; IL-4: interleukin-4; Th₁: helper T cell type 1; Th₂: helper T cell type 2; IL-2: interleukin-2; IL-10: interleukin-10; IL-5: interleukin-5; IFN-λ: interferon-λ; IFNLR1: interferon-lambda receptor 1; IL10Rβ: interleukin-10 receptor beta; IFNλR: interferon-lambda receptor; NK cell: natural killer cell.