Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor

Abstract

Human exposure to Pneumocystis carinii is common but, in the absence of acquired or genetic dysfunction of either cellular or humoral immunity, exposure rarely leads to illness. Although alveolar macrophages can degrade P. carinii, macrophage receptors involved in P. carinii recognition have not been clearly defined. Characterization of a predominant surface glycoprotein of the high mannose type led us to investigate the role of the macrophage mannose receptor in this process. We report here that binding and uptake of cultured rat P. carinii by human and rat alveolar macrophages is reduced by 90% in the presence of competitive inhibitors of mannose receptor activity and by adherence of alveolar macrophages to mannan-coated surfaces. Further, only those COS cells transfected with the human macrophage mannose receptor complementary DNA that express surface mannose receptors bind and ingest P. carinii. These studies establish that the macrophage mannose receptor is sufficient for uptake of P. carinii and emphasize the role of the alveolar macrophage in first-line host defence against P. carinii.

Synergistic regulation of Pseudomonas aeruginosa‐induced cytokine production in human monocytes by mannose receptor and TLR2

“…MR, a well-characterized receptor, has been reported to bind a wide variety of pathogens including Candida albicans [30], Leishmania donovani [38], Pneumocystis carinii [39], and Mycobacterium tuberculosis [40]. Moreover MR has been recognized as a phagocytic receptor of non-opsonized P. aeruginosa bacteria [33].…”

Antibody-targeted vaccines

“…A characteristic feature shared by many CLRs is their endocytic capacity and the presence of carbohydrate recognition domains (CRDs). The CRDs can selectively bind to glycans associated with microorganisms and lead to rapid internalization (Ezekowitz et al, 1991;Brown et al, 2003;Mansour et al, 2006). This process can initiate effective immune defense, although some pathogens may subvert this pathway and suppress beneficial immune responses (Turville et al, 2003;van Kooyk et al, 2004).…”

Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia

“…Several surface molecules on alveolar macrophages have been shown to interact with Pneumocystis, including Fc-gamma receptor, [5] complement receptor, [6] scavenger receptor, [7] mannose receptor, [8] and dectin-1. [9] TLR2 is a pattern recognition receptor recognizing a large variety of ligands such as peptidoglycan, lipoprotein, lipopeptide, and zymosan.…”