Innate versus adaptive immunity in Candida albicans infection.

Candida albicans is a common opportunistic pathogen, causing both superficial and systemic infection. Clinical observations indicate that mucocutaneous infections are commonly associated with defective cell-mediated immune responses, whereas systemic infection is more frequently seen in patients with deficiencies in neutrophil number or function. Analysis of mechanisms of host resistance against gastrointestinal and oral infection in mouse models has demonstrated an absolute dependence on CD4(+) T cells, although clearance also involves phagocytic cells. Both IL-12 and TNF-alpha appear to be important mediators, but mouse strain-dependent variations in susceptibility to infection may be related to T-cell enhancement of production of phagocytic cells by the bone marrow. In murine systemic infection, the role of innate and adaptive responses is less well defined. Studies in immunodeficient and T-cell-depleted mice suggest that clearance of the yeast may be predominantly a function of the innate response, whereas the adaptive response may either limit tissue damage or have the potential to cause immunopathology, depending on the host genetic context in which the infection takes place.

Bone marrow colony-formation in vitro after infection of genetically defined inbred mice with Candida albicans.

The effect of C. albicans infection on the production of haematopoietic precursor cells in the bone marrow of CBA/CaH and BALB/c mice was evaluated by assay of colony formation in vitro. In immunocompetent mice, neither systemic nor oral infection induced significant alterations in colony formation by bone marrow from the two mouse strains, and Candida infection did not alter the proportion of morphological cell types in the colonies. However, the number of neutrophil-like was relatively greater in colonies derived from acutely infected CBA/CaH nude mice than in those from BALB/c nude mice, whereas small mononuclear cells were present in higher proportions in the latter strain. In both strains of nude mice, there was an increase in colony formation at 6 days after oral infection, but at 8 weeks, when the infection had become chronic, the production of bone marrow cells by CBA/CaH nude mice was significantly less than that by BALB/c nude mice. Reconstitution of nude mice with syngeneic lymphocytes enhanced the production of bone marrow precursor cells by BALB/c, but not by CBA/CaH mice, suggesting that T cells can enhance host resistance by promoting the colony-forming response of the bone marrow in BALB/c mice that are genetically resistant to tissue damage, but not in CBA/CaH that are prone to severe lesions. Finally, culture with Candida antigen in vitro decreased the number of colony-forming cells in cultures from CBA/CaH, but not from BALB/c mice.