Th1‐Th2 Cytokine Kinetics in the Bronchoalveolar Lavage Fluid of Mice Infected with Cryptococcus neoformans of Different Virulences

Abstract

Th 1 immune response plays an important role in protection against infection with Cryptococcus neoformans in mice. We investigated the effect of virulence of C. neoformans on cytokine production in the lung of a mouse model of pulmonary cryptococcosis. BALB/c mice were inoculated intratracheally with a high or low virulence strain of C. neoformans, followed by serial measurements of Thl and Th2 cytokine concentrations in the bronchoalveolar lavage (BAL) fluid using appropriate enzyme-linked immunosorbent assay kits. The number of colony-forming units (CFU) increased with time, and all mice infected with the highly virulent strain were dead at 28 days after inoculation. In contrast, the number of microorganisms diminished with time in the mice infected with the low virulence strain during the 4-week study. The numbers of neutrophils and lymphocytes in the BAL fluid paralleled those of CFU. High neutrophil counts were observed in the BAL fluid of mice infected with the highly virulent strain, while lymphocyte counts were increased only in the later part of the study in mice infected with the high and low virulence strains. The concentrations of Th2 cytokine, interleukin (IL)-4 were significantly higher in mice infected with the highly virulent strain at days 14 and 21 of infection, whereas the level of Thl cytokine, interferon-gamma, was significantly higher in the latter strain at days 7 and 14. Our results suggest that strain-specific difference in the organism's ability to induce (or evade) the host immune system contributes to the outcome of infection.

Therapeutic Efficacy of a Conjugate Vaccine Containing a Peptide Mimotope of Cryptococcal Capsular Polysaccharide Glucuronoxylomannan

“…In the light of our previous observation suggesting that P13 conjugates enhance innate immune mechanisms (42), as well as evidence that Th1-like immunity is important for host defense against cryptococcosis (60,62), we compared the expression of IFN-␥ (31, 68) and IL-10, an immunosuppressive cytokine that is linked to Th2-like immune responses (17,46), in P13-protein conjugate and control mice. In consonance with the evidence that cryptococcosis develops in the setting of a Th2-like bias (2,33,54), we observed more expression of IL-10 than IFN-␥ in all experimental groups. Naïve C57BL/6 mice had higher baseline cytokine expression levels than naïve BALB/c mice, but the mean integral IL-10/IFN-␥ ratio was similar for both strains.…”

Potential contribution of fungal infection and colonization to the development of allergy

“…In mice, cryptococcal virulence is linked to the ability to promote Th2 polarization [95,96]. Infection-related IL-12 suppression and enhancement of IL-10 production have been observed [97,98].…”

Cryptococcus neoformansDirectly Stimulates Perforin Production and Rearms NK Cells for Enhanced Anticryptococcal Microbicidal Activity

“…In this regard, C. neoformans can modulate immune responses by blocking phagocytosis, inducing lymphocyte apoptosis, and inducing immunosuppressive cytokine secretion (42,54,59). Importantly, C. neoformans is able to skew the cytokine milieu to a Th2-type response (1). This prolongs the survival of the fungus as a Th1 immune response is necessary for optimal host defense against the fungus (17).…”