Mucosal and systemic candidiasis in congenitally immunodeficient mice

Abstract

Colony counts and light microscopy were used to assess the capacity of Candida albicans to colonize, infect the alimentary tract, and cause disseminated disease in athymic (nulnu), euthymic (nul+), beige (bglbg), black (bgl+), beige athymic (bglbg nulnu), or beige euthymic (bglbg nul+) germfree mice. The alimentary tracts of all six genotypes of germfree mice were quickly colonized after exposure to yeast-phase C. albicans. Only bglbg nu/nu mice showed obvious morbidity and mortality after mucosal colonization with C. albicans. Histopathology of C. albicans-colonized immunocompetent (nu/+, bgl+) and singly immunodeficient (nu/nu, bglbg, bglbg nul+) mice showed minimal to moderate mucosal infections, whereas doubly immunodeficient (bglbg nu/nu) mice showed extensive yeast and hyphal infection of the palate, tongue, esophagus, and stomach. A progressive systemic infection in C. albicans-colonized mice occurred only in bglbg nulnu mice 12 to 16 weeks after colonization and mucosal infection. Thus, it appears that a combination of defective cell-mediated immunity and phagocytic cell defects (polymorphonuclear leukocytes and/or macrophages) predisposed mice to severe mucosal and systemic candidiasis of endogenous origin. This is the first report of a mouse strain that is not only naturally susceptible to mucosal and systemic candidiasis of endogenous origin but also shows lethality at early (1 to 4 weeks) and late (12 to 16 weeks) times after alimentary tract colonization. tively) females.GF mice were originally derived from NIH BALB/c nude mice, NIH C57BL/6 beige mice, and N:NIH(S) III beige athymic mice by cesarean derivation and have since been 1093 on August 5, 2020 by guest

Differential role of NK cells against Candida albicans infection in immunocompetent or immunocompromised mice

“…Using an alimentary tract infection model, others have shown that genetically deficient Tgε26mice, that are deprived of both T and NK cells, are unable to control a lethal oroesophageal candidiasis . Finally, combined genetic deficiencies in NK, phagocytic and T cells (beige nude mice) predispose mice to severe mucosal and disseminated candidiasis of endogenous origin . Thus, NK cells do seem to play an essential role in severe disseminated candidiasis in hosts devoid of a functional adaptive immune system.…”

Nitric oxide‐enhanced resistance to oral candidiasis

“…Numerous studies indicate that T cells (through cytokine activation of macrophages and neutrophils) play an important role in the resistance to infection with C. albicans. 26,27 The generation of NO is regulated by Th1 and Th2 cells and their secreted cytokines, such as IFN-c and IL-4. For example, loss of iNOS expression and the consequent defective production of NO led to an increase in the Th1 response, 28 whereas NO enhanced the expression of the Th2 cytokine, IL-4.…”

Intestinal Lesions Associated with Disseminated Candidiasis in an Experimental Animal Model

“…In order to study candidiasis arising from the gastrointestinal tract, orally inoculated animals have been used. Oral inoculation of infant mice (10,30), mice treated with antibiotics or immunosuppressive drugs (7,8,13), or immunodeficient mice (4,20) has resulted in gastrointestinal colonization and some level of dissemination of the organism to internal organs. Invasion of the cardiac-atrial fold of the stomach was seen in infant mice, but intestinal lesions were not observed.…”