Th1 and Th2 cytokine secretion patterns in murine candidiasis: association of Th1 responses with acquired resistance

Abstract

Two chemically mutagenized agerminative variants of Candida albicans were used to immunize mice against challenge with highly virulent cells of the parent strain. Although both mutants (Vir-3 and Vir-13) resulted in nonlethal infection and could be recovered from mouse organs for many days after the intravenous inoculation of 10' to 106 cells, significant protection to systemic challenge with virulent C. albicans was induced by only one (Vir-3) of the two variants. Anticandidal resistance in Vir-3-infected mice was associated with the occurrence in vivo of strong delayed-type hypersensitivity to Candida antigen, detection in vitro of highly fungicidal effector macrophages, and presence in the serum of a large proportion of Candida-reactive antibodies of the immunoglobulin G2a isotype. Bulk cultures of purified CD4+ lymphocytes from mice infected with either mutant were compared for their ability to produce gamma interferon (IFN-y), interleukin-2 (IL-2), IL-4, and IL-6 in vitro. After stimulation with specific antigen, CD4+ cells from Vir-3-immunized mice released large amounts of the Thl-specific cytokines, IFN-'y and IL-2, at a time when CD4+ cells from Vir-13-infected mice predominantly secreted the characteristic Th2 cytokines, IL-4 and IL-6. These results were confirmed by quantitative analysis of cytokine-producing Thl and Th2 cells. In addition, only mice infected with Vir-3 displayed a high frequency of CD8+ cells with the potential for in vitro lysis of yeast-primed bone marrow macrophages. Purified CD4+ cells from Vir-3-infected mice, but not a mixture of these cells with CD4+ lymphocytes from mice infected with Vir-13, could adoptively transfer delayed-type hypersensitivity reactivity onto naive mice. Taken together, these data suggest that both Thl and Th2 CD4+ lymphocytes may be activated during experimental C. albicans infection in mice.

Chronic mucocutaneous candidiasis. I. Altered antigen-stimulated IL-2, IL-4, IL-6 and interferon-gamma (IFN-γ) production

“…These findings suggest that the immune defects seen in CMC are perhaps not as selective or subtle as previously supposed. Data obtained on animal (murine) models have shown that resistance to systemic and mucosal candidiasis is closely associated with a Th1 type of response characterized by increased production of IFN-, IL-2, and enhanced DTH, while susceptibility is accompanied by a Th2 type response with increased IL-4 and IL-6 production [8]. Administration of anti-IL-4 antibody in this model resulted in increased survival [9].…”

Effects of glycyrrhizin, an active component of licorice roots, onCandida albicansinfection in thermally injured mice

“…Non-specific immune responses, expressed by activation of polymorphonuclear neutrophils [28][29][30] and macrophages [31,32], have been shown to be involved in the resistance to the early phase infection with C. albicans. A major influence in host resistance against systemic C. albicans infection is a type 1 T cell-associated cellular response (type 1 T cell response) [33][34][35][36][37][38]. Type 1 T lymphocytes produce type 1 cytokines (IL-2 and IFN-g) following appropriate stimulation [34].…”

“…Type 1 T lymphocytes produce type 1 cytokines (IL-2 and IFN-g) following appropriate stimulation [34]. These type 1 cytokines are able to activate and enhance killing activities of effector cells (cytotoxic T lymphocytes, natural killer cells, macrophages and neutrophils) targeted to cells infected with C. albicans [34][35][36][37][38][39]. However, type 1 T cell responses are generally suppressed by type 2 cytokines (IL-4 and IL-10) [40][41][42] released from T helper type 2 cells (Th2 cells) or CD8 þ type 2 T cells [43][44][45].…”

Association between atopy and recurrent vaginal candidiasis

“…The association between vaginal candidiasis with a type 2 immune response has been well documented in experimental models of candidiasis. While in the CBA/j mice, a type 1 immune response is generated with subsequent control of infection, BALB/c mice produce predominantly IL-4 and have recurrent infections [10]. This may imply that type 1 immune reactivity is associated with resistance to candidal disease, while type 2 immune responses are associated with pathology of RVC.…”