Correlation between in vivo and in vitro studies of modulation of resistance to experimental Candida albicans infection by cyclophosphamide in mice

Abstract

Mice receiving a single injection of cyclophosphamide (150 mg/kg) 1 to 6 days before inoculation with viable Candida albicans showed an increased susceptibility to the challenge accompanied by a reduction in peripheral blood polymorphonuclear leukocytes and lymphocytes as well as in spleen cellularity. Several immunological in vitro functions also appeared to be dramatically depressed. Most of these hematological and functional parameters returned to control values by day 9 after cyclophosphamide administration, at a time when resistance to C. albicans infection appeared to be unchanged. However, when exposure to cyclophosphamide occurred 12 to 21 days before inoculation with the live yeast, enhanced resistance was observed with the majority of the animals surviving challenge. To gain some insight into the mechanisms underlying this late increase in resistance to C. albicans infection after cyclophosphamide administration, we analyzed a series of immunological functions, including the in vitro candidacidal activity of polymorphonuclear neutrophils and plastic-adherent and nonadherent spleen cells as well as the activity of natural killer cells and alloreactive T lymphocytes. The results show that a numerical rebound of blood polymorphonuclear neutrophils and the appearance of a highly candidacidal cell population in the spleen may be among the factors underlying the late increase in resistance to C. albicans after administration of cyclophosphamide.

Role of trehalose in resistance to macrophage killing: study with a tps1/tps1 trehalose-deficient mutant of Candida albicans

“…Studies using murine models of disseminated candidiasis have demonstrated that macrophages play an important role in host resistance [12–14]. Macrophages are phagocytic cells of the immune system that are able to recognise and eliminate microorganisms crossing the epithelial barrier.…”

Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice

“…Although the importance of T-cell-dependent immunity in chronic mucocutaneous candidosis has been clearly established (12,29,34,50), the protective role of this component of immunity in systemic candidosis has not been so well defined (13,23,46). As a matter of fact, innate natural immune mechanisms appear to be most important in resistance to disseminated C. albicans infections, with a major role apparently being played by nonspecifically activated polymorphonuclear leukocytes (PMN) (2,6,23,33,47) and macrophages (1,3,5,30,43).…”

Heterogeneous activity of immature and mature cells of the murine monocyte-macrophage lineage derived from different anatomical districts against yeast-phase Candida albicans

“…For the past few years our group has been studying systemic acute C. albicans infections in normal and immunomodulated mice (4,8). In this particular model of systemic challenge, the role played by the natural defense mechanisms in reducing the invading pathogenic burden seems to be decisive.…”