Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies

Figure 1

Schematic representation of the host immune response against microbial pathogens. Microbial pathogens or antigens can be taken up by the antigen-presenting cells, mostly dendritic cells (DCs), once they breach the epithelial barrier. Antigens are presented to the naive T cells by the activated DCs through major histocompatibility complex–T cell receptor interaction, which leads to activation and expansion of antigen-specific effector T cells (Teff). Teff differentiate into one of the different subtypes, e.g., helper T cells (Th)1, Th2, follicular helper T cells (Tfh), Th17, or regulatory T cells (Tregs), depending on the cytokine milieu of the microenvironment. Th1 cells activate macrophages or CD8⁺ T cells through production of IFN-γ. Activated macrophages fuse their lysosomes more efficiently to phagosomes, exposing intracellular microbes to a variety of microbicidal lysosomal enzymes and toxic oxygen and nitrogen metabolites. Cytotoxic T cells (CTL) destroy pathogens through release of perforins and granzymes or induce apoptosis of infected cells. Th2 and Tfh cells activate B cells through production of cytokines and induce the differentiation of B cells into plasma cells, antibody class switching, and affinity maturation of antibodies, which remove the pathogen by neutralization, opsonization, and phagocytosis. Th17 cells participate in neutrophil activation and immune regulation by producing cytokine IL-17A, which is required for protection against extracellular and some intracellular pathogens. Tregs regulate immune responses to pathogens and maintain self-tolerance by negatively regulating Th1 and Th2 cells, e.g., by producing cytokines IL-10 and TGF-β. Innate immune cells such as eosinophils, basophils, and mast cells play an important role in protection against parasitic infections including helminth infections. Natural killer (NK) and natural killer T (NKT) cells, which form a bridge between innate and adaptive immunity, also contribute to antibacterial and antiviral immunity. NK cells have similar functions as the CTL while NKT cells produce cytokines to execute their killing functions.