Characteristics of Invasive Candidiasis in Gamma Interferon- and Interleukin-4-Deficient Mice: Role of Macrophages in Host Defense againstCandida albicans

Abstract

Murine models of invasive candidiasis were used to study the in vivo importance of gamma interferon (IFN-γ) and interleukin-4 (IL-4) in host defense against Candida albicans and to characterize the tissue inflammatory reactions, with special reference to macrophages (Mφ). Knockout (KO) IFN-γ-deficient (GKO) and IL-4-deficient (IL-4 KO) and C57BL/6 parental mouse strains were challenged intraperitoneally with 108 C. albicans blastoconidia. Survival of GKO mice was significantly lower (16.7%) than that of C57BL/6 control (55.5%) and IL-4 KO (61.1%) animals, but was not correlated with the extent of organ colonization. Immunohistological analysis with a panel of myeloid and lymphoid markers revealed multiple renal abscesses, myocarditis, hepatitis, meningoencephalitis, and pneumonia in each strain, with a dominant presence of Mφ. In the absence of IFN-γ, C. albicans induced striking changes in the phenotype of alveolar Mφ and extensive perivascular lymphoid infiltrates in the lung. Impairment in nitric oxide production by peritoneal Mφ was shown only in GKO mice, and they produced Candida-specific immunoglobulin G (IgG), IgM, IgA, and IgG subclasses in lower titers. Our in vivo studies with KO mice elucidate a critical role for IFN-γ, but not IL-4, in host defense against C. albicans.

Severe Impairment in Early Host Defense againstCandida albicans in Mice Deficient in Myeloperoxidase

“…In the wild-type mice, the highest and lowest numbers of fungi were found in the liver and the brain, respectively (Fig. 8), consistent with a previous report (20). In contrast, significantly higher numbers of fungi were disseminated into every organ in the homozygous mutant mice, and approximately 290, 11, 110, 17, and 10 times as many viable fungi were cultured from the lungs, brain, kidneys, spleen, and liver, respectively (Fig.…”

The Importance of the Phagocytes' Innate Response in Resolution of the Infection Induced by a Low Virulent Candida albicans Mutant

“…Despite the crucial role of neutrophils in controlling the initial candidaemia and systemic spread of the yeast, the dominance of macrophages over neutrophils in the tissue infiltrates during early stages of the infection [58] confirms that these cells play a key role in the host response to C. albicans. After analysing the contribution of macrophages in an in vitro model of phagocytosis, we detected that activation is crucial for the elimination of CM1613, while SC5314 cannot be destroyed as efficiently as the mutant strain although macrophages were activated.…”

Low dose of Concanavalin-A enhances innate immune response and prevents liver injury in mice infected withCandida albicans

“…Various virulence factors contribute to pathogenesis; for example aspartyl proteases and phospholipases play an essential early role in C. albicans dissemination and enhance its ability to colonize deep organs (Fallow et al, 1997;Calderone & Fonzi, 2001), adhesins allow adherence to epithelial and endothelial cells (Naglik et al, 2003), and morphogenesis consists of reversible transitions between unicellular yeast cells and the filamentous growth forms that are present in clinical lesions (Kobayashi & Cutler, 1998;Romani et al, 2003;Consolaro et al, 2005). It has been demonstrated that Th cell reactivity plays a central role in regulating the immune response to C. albicans, Th1 reactivity being responsible for resistance and Th2 reactivity being associated with susceptibility (Nomi et al, 1994;Kaposzta et al, 1998;Romani, 1999).…”