Pathological and protective immunity to Pneumocystis infection

Abstract

Pneumocystis jirovecii is a common opportunistic infection in the HIV-positive population and is re-emerging as a growing clinical concern in the HIV-negative immunosuppressed population. Newer targeted immunosuppressive therapies and the discovery of rare genetic mutations have furthered our understanding of the immunity required to clear Pneumocystis infection. The immune system can also mount a pathologic response against Pneumocystis following removal of immunosuppression and result in severe damage to the host lung. The current review will examine the most recent epidemiologic studies about the incidence of Pneumocystis in the HIV-positive and HIV-negative populations in the developing and developed world and will detail methods of diagnosis for Pneumocystis pneumonia. Finally, this review aims to summarize the known mediators of immunity to Pneumocystis and detail the pathologic immune response leading to Pneumocystis-related immune reconstitution inflammatory syndrome.

Figure 1

Radiographic and microbiologic diagnosis of Pneumocystis. A. Chest radiograph of child with X-linked severe combined immunodeficiency showing bilateral ground glass infiltrates (white arrows) and air bronchograms consistent with Pneumocystis pneumonia. Note that this patient also has a pneumomediastinum (red arrow) with air dissecting into the soft tissue of the neck and an absent thymic shadow in the mediastinum consistent with athymia. B. Gomori-methenamine silver stain (GMS) on Pneumocystis infected mouse lung, showing lung architecture (green) with Pneumocystis organisms (black) filling the alveolar spaces.

Figure 2

Model of Immune Reconstitution Inflammatory Syndrome. In a patient with less than 200 cells/uL of CD4⁺ T cells, Pneumocystis (PC) can propagate in the lungs and produce high PC burdens. Following reconstitution, high levels of PC asci or PC antigen can persist in the lungs and lead to activation of T cells through IL-2, which can induce apoptosis in the absence of regulatory T cell (Treg) inhibition. The lack of Tregs also allows for increased inflammatory cell recruitment due to PC and resultant surfactant changes, leading to systemic release of pro-inflammatory cytokines.