Abstract: Pneumocystis jirovecii pneumonia (PJP) is a high-burden opportunistic infection with a significant risk of death among immunocompromised hosts. Pneumocystis spp. cycle between trophic forms and cysts within the host alveoli. The trophic form relies heavily on the folate biosynthesis pathway, whereas the cyst form, supported by a β-1,3-glucan-rich cell wall, is considered important for transmission. Immune evasion is mediated in part by major surface glycoprotein antigenic variation, and additional effects on host antigen-presentation pathways have been reported primarily in experimental rodent models and remain to be established in human disease. Innate recognition mediated by Dectin-1, with additional contributions from Toll-like receptor 2 (TLR2) signaling described in experimental models, may promote T helper 17 (Th17)- and Th1-biased immune responses. Distinct host immune contexts then shape divergent disease phenotypes. In HIV-infected hosts, CD4+ T-cell deficiency, high fungal burden, and impaired clearance predominate, and immune reconstitution inflammatory syndrome (IRIS) may occur early after initiation of antiretroviral therapy (ART). In non-HIV immunocompromised hosts, broader immune dysfunction, including impaired antibody responses and antigen presentation together with complement and neutrophil activation, more often leads to a low-burden but highly inflammatory pattern that can progress to acute respiratory distress syndrome (ARDS). This review summarizes the life cycle, adhesion and immune pathways, immune evasion mechanisms, and differences between HIV-infected hosts and non-HIV immunocompromised hosts, with the goal of supporting precision treatment for PJP and optimizing clinical strategies. Keywords: Pneumocystis jirovecii , HIV-associated immunodeficiency, non-HIV immunocompromised hosts, innate immunity, adaptive immunity, immunopathogenesis
Wang et al. (Wed,) studied this question.