Abstract Dendritic cells (DCs), a vital component of the innate immune system, are considered to lack antigen specificity and be devoid immunological memory. Strategies that can induce memory-like responses from utilized elicit protective immunity in deficient persons. Here we utilize an experimental immunization strategy modulate DC inflammatory against opportunistic fungal pathogen causes significant disease immunocompromised individuals. Our results show DCs isolated protectively...

ABSTRACT Calcineurin is a calcium-activated protein phosphatase that the target of immunosuppressants cyclosporin A and FK506. In T cells, calcineurin controls nuclear import NF-AT transcription factor gene activation. plants fungi, functions in stress responses (e.g., temperature, cations, pH) necessary for virulence fungal pathogen Cryptococcus neoformans . Here we show also required another major fungus pathogenic to humans, Candida albicans. C. albicans mutants had significantly reduced...

We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary infection with Cryptococcus neoformans strain engineered to produce the Th1-type cytokine gamma interferon (IFN-gamma). Mice an IFN-gamma-producing C. were able resolve primary and demonstrated complete (100%) protection against second challenge pathogenic strain. Pulmonary analyses showed that Th1-type/proinflammatory chemokine expression significantly higher Th2-type was lower infected compared wild-type-infected...

Vulvovaginal candidiasis (VVC) caused by Candida albicans affects a significant number of women during their reproductive ages. Clinical observations revealed that robust vaginal polymorphonuclear neutrophil (PMN) migration occurs in susceptible women, promoting pathological inflammation without affecting fungal burden. Evidence to date the mouse model suggests similar acute PMN into vagina is mediated chemotactic S100A8 and S100A9 alarmins produced epithelial cells response Candida. Based...

Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening pneumonia and meningoencephalitis in immune compromised individuals. Previous studies have shown immunization of BALB/c mice with IFN-gamma-producing C. strain, H99gamma, results complete protection against a second pulmonary challenge otherwise lethal cryptococcal strain. The current study evaluated local anamnestic cell-mediated responses cryptococcosis immunized strain H99gamma compared to heat-killed...

Abstract Experimental pulmonary Cryptococcus neoformans infection in BALB/c mice is associated with polarized Th2-type cytokine production, alternative macrophage activation, and severe bronchopneumonia. In contrast, a C. strain that secretes IFN-γ, H99γ, elicits Th1-type production classical activation. Additionally, infected H99γ resolve the acute are subsequently protected against challenge wild-type neoformans. The present study characterizes activation during protective response to...

The current studies evaluated the role of interleukin (IL)-17A in induction protective immunity against pulmonary cryptococcosis mice. Protection infection with C. neoformans strain H99γ was associated increased IL-17A production. Signaling through IFN-γ receptor (R) required for production, however, a Th17-type cytokine profile not observed. Neutrophils were found to be predominant leukocytic source IL-17A, rather than T cells, suggesting that produced part cell-mediated immune response....

ABSTRACT Cryptococcus neoformans , the predominant etiological agent of cryptococcosis, is an opportunistic fungal pathogen that primarily affects AIDS patients and undergoing immunosuppressive therapy. In immunocompromised individuals, C. can lead to life-threatening meningoencephalitis. Studies using a virulent strain engineered produce gamma interferon (IFN-γ), denoted H99γ, demonstrated protection against pulmonary infection associated with generation T helper 1 (Th1)-type immune...

Since its original isolation in 2009, Candida auris has spread across the globe as a causative agent of invasive candidiasis. C. is typically intrinsically resistant to fluconazole and can also be echinocandins even amphotericin B. Thus, there an urgent need find new treatment options against this emerging pathogen. To address growing problem, we performed screen Prestwick Chemical library, repurposing library 1,280 small molecules, consisting mostly approved off-patent drugs, search those...

Repositioning old drugs can significantly decrease the time and effort that it takes to develop novel antifungal therapeutics, which represents a pressing unmet clinical need due devastating nature of fungal infections. We have previously described activity auranofin, gold thiol compound used treat rheumatoid arthritis, against Candida albicans biofilms. Here we evaluate its spectrum action describe variety medically important fungi.

ABSTRACT Morphological switch is tightly coupled with the pathogenesis of many dimorphic fungal pathogens. Cryptococcus neoformans , major causative agent cryptococcal meningitis, mostly presents as yeast form but capable switching to hyphal form. The filamentous has long been associated attenuated virulence, yet underlying mechanism remains elusive. We previously identified master regulator Znf2 that controls yeast-to-hypha transition in . Activation promotes formation and abolishes...

Abstract Nonprotective immune responses to highly virulent Cryptococcus neoformans strains, such as H99, are associated with Th2-type cytokine production, alternatively activated macrophages, and inability of the host clear fungus. In contrast, experimental studies show that protective against cryptococcosis Th1-type production classical macrophage activation. The response induced during C. strain H99γ (C. H99 engineered produce murine IFN-γ) infection correlates enhanced phosphorylation...

Development of vaccines against opportunistic infections is difficult as patients most at risk developing disease are deficient in aspects the adaptive immune system. Here, we utilized an experimental immunization strategy to induce innate memory macrophages vivo. Unlike current trained immunity models, present memory-like phenotype that maintained for least 70 days post-immunization and results complete protection secondary challenge absence cells. RNA-seq analysis vivo IFN-γ primed...

In Candida albicans, calcineurin is essential for virulence and survival during membrane perturbation by azoles. Crz1 a proposed downstream target of based on studies Saccharomyces cerevisiae. However, the in vitro phenotypes C. albicans crz1/crz1 mutants differ not required virulence.

Protective responses in mice immunized with an interferon-gamma producing strain of Cryptococcus neoformans, H99γ, are associated IL-17A production by neutrophils. Neutrophil depletion H99γ-immunized did not affect pulmonary fungal burden, indicating that neutrophils required for clearance. However, we observed increase the lungs neutrophil-depleted H99γ infected mice, which corresponded to IL-17A+ γδ+ T cells. Moreover, increased IL-17A+/ CD3+ cells and IL-17A+/γδ+ cells, but decreased...

ABSTRACT Individuals with defects in T cell-mediated immunity (CMI) are highly susceptible to infection Cryptococcus neoformans . The purpose of these studies was determine if protection against experimental pulmonary cryptococcosis can be generated cell-deficient hosts. BALB/c mice were depleted CD4 + and/or CD8 cells or given an isotype control antibody prior vaccination a C. strain, designated H99γ, previously shown induce immunocompetent mice. Mice cells, but not both subsets, survived...

The human fungal pathogen, Cryptococcus neoformans, dramatically alters its cell wall, both in size and composition, upon entering the host. This wall remodeling is essential for host immune avoidance by this pathogen. In a genetic screen mutants with changes their we identified novel protein, Mar1, that controls organization evasion. Through phenotypic studies of loss-of-function strain, have demonstrated mar1Δ mutant has an aberrant surface defect polysaccharide capsule attachment,...

Numerous virulence factors expressed by Cryptococcus neoformans modulate host defenses promoting nonprotective Th2-biased adaptive immune responses. Prior studies demonstrate that the heat shock protein 70 homolog, Ssa1, significantly contributes to serotype D C. through induction of laccase, a Th2-skewing and CNS tropic factor. In present study, we sought determine whether Ssa1 modulates in mice infected with highly virulent A strain (H99). To investigate this, assessed pulmonary fungal...