Current Understanding of Pneumocystis Immunology

Abstract

Pneumocystis jirovecii is the opportunistic fungal organism that causes Pneumocystis pneumonia (PCP) in humans. Similar to other opportunistic pathogens, Pneumocystis causes disease in individuals who are immunocompromised, particularly those infected with HIV. PCP remains the most common opportunistic infection in patients with AIDS. Incidence has decreased greatly with the advent of HAART. However, an increase in the non-HIV immunocompromised population, noncompliance with current treatments, emergence of drug-resistant strains and rise in HIV+ cases in developing countries makes Pneumocystis a pathogen of continued interest and a public health threat. A great deal of research interest has addressed therapeutic interventions to boost waning immunity in the host to prevent or treat PCP. This article focuses on research conducted during the previous 5 years regarding the host immune response to Pneumocystis, including innate, cell-mediated and humoral immunity, and associated immunotherapies tested against PCP.

Pneumocystis jirovecii Pneumonia in AIDS Patients

“…Alveolar macrophages are the first line of host defence to control the infection, since they are the principal phagocytes mediating the uptake and direct degradation of both trophic forms and cysts forms in the lung (Kelly & Shellito, 2010). Macrophages display several potential receptors for glucans, including CD11b/CD18 integrin (CR3), dectin-1, and toll-like receptor 2.…”

“…Neutrophils are associated with inflammation and, therefore, have been implicated in severity of disease. In fact, decreased pulmonary function and local lung inflammation and damage have been correlated with elevated neutrophil counts in HIV-infected patients with PcP (Kelly & Shellito, 2010). The neutrophils recruited into the lungs release reactive oxidant species, proteases, and cationic proteins, which directly injure capillary endothelial cells and alveolar epithelial cells (Thomas & Limper, 2004).…”

“…This cytokine is produced primarily by CD4+ T cells. There is an indirect correlation between IFN-levels and severity of PcP (Kelly & Shellito, 2010). IFN-strongly activates the macrophage production of TNF-, superoxides, and reactive nitrogen species, each of which is implicated in the host defence against Pneumocystis (Wright et al, 1999a).…”

“…In addition, the time course of chemokine expression correlates Pneumocystis clearance, but also with the lung inflammation (Wright et al, 1999a). Thus, the role of chemokines is essential for the resolution of infection, but overexpression may also result in a hyperinflammatory state and lung damage (Kelly & Shellito, 2010).…”

Pneumocystis jirovecii Rtt109, a Novel Drug Target for Pneumocystis Pneumonia in Immunosuppressed Humans

“…The reported mortality rates for PcP range between 10 and 30% for AIDS patients and between 30 and 70% for selected non-HIV-infected patients with immunosuppression (8)(9)(10)(11)(12)(13). Several factors contribute to poor PcP outcomes, including delayed diagnosis (14,15) and complex host-pathogen interactions (16)(17)(18)(19)(20)(21). Like other opportunistic fungal pathogens, there is also the emerging threat of Pneumocystis populations developing resistance to the currently available therapeutic agents (22)(23)(24).…”