Macrophages in resistance to candidiasis

Abstract

Candida albicans, an increasingly common opportunistic pathogenic fungus, frequently causes disease in immunodeficient but not immunocompetent hosts. Clarifying the role of the phagocytic cells that participate in resistance to candidiasis not only is basic to understanding how the host copes with this dimorphic pathogen but also will expedite the development of innovative prophylactic and therapeutic approaches for treating the multiple clinical presentations that candidiasis encompasses. In this review, we present evidence that a diverse population of mononuclear phagocytes, in different states of activation and differentiation and from a variety of host species, can phagocytize C. albicans blastoconidia via an array of opsonic and nonopsonic mechanisms and can kill C. albicans blastoconidia and hyphae by means of oxygen-dependent and -independent mechanisms. Reactive nitrogen intermediates should now be added to the well-established candidacidal reactive oxygen intermediates of macrophages. Furthermore, what were thought to be two independent pathways, i.e., nitric oxide and superoxide anion, have now been shown to combine to form a potent macrophage candidacidal molecule, peroxynitrite. In contrast to monocytes and neutrophils, which are important in resistance to early stages of C. albicans infections, more differentiated macrophages activated by cytokines such as gamma interferon participate in the acquired resistance of hosts with C. albicans-specific, cell-mediated immunity. Evidence presented in this review demonstrates that mononuclear phagocytes, in some instances in the absence of other professional phagocytes such as neutrophils, play an import role in resistance to systemic and mucosal candidiasis.

RAD51–WSS1-dependent genetic pathways are essential for DNA–protein crosslink repair and pathogenesis in Candida albicans

“…The interaction between C. albicans and innate immune cells such as macrophages and neutrophils is key to either fungal clearance or survival leading to pathogenesis ( 42 , 43 ). Since the cell wall of C. albicans acts as an interface between the fungus and host cells, the morphological modification of DPCR-deficient cells could affect its pathogenicity.…”

Histone Acetylation Regulator Gcn5 Mediates Drug Resistance and Virulence of Candida glabrata

“…As a successful human pathogen, C. glabrata is highly adapted to interaction with host cells and the immune response. Macrophages are professional phagocytes that act as part of the innate immune system of the host, contributing to antifungal defense via phagocytosis and clearance of invading fungal pathogens ( 34 ). Phagocytosis of C. glabrata starts with pattern recognition of fungal cell wall components such as β-glucan and mannan by the C-type lectin receptors dectin-1 and dectin-2 on macrophages ( 35 , 36 ).…”

Functionality of the human antibody response to Candida albicans

“…This can occur independently of immune cells by a mechanism resembling neutralization, as shown here. In vivo , opsonization additionally supports protection by increasing pathogen recognition by phagocytic cells [ 32 , 33 ]. Evidently, the immunological potential of an anti- Candida antibody response will, under normal circumstances, be redundant with the capacity of other immune components (especially neutrophils as main effector cells of the innate immune system [ 34 , 35 ]) to clear the fungus, explaining the lack of enhanced C. albicans susceptibility in patients lacking B cells or antibodies [ 36 , 37 ].…”