Innate and adaptive antifungal immune responses: partners on an equal footing

Abstract

Adaptive immunity has long been regarded as the major player in protection against most fungal infections. Mounting evidence suggest however, that both innate and adaptive responses intricately collaborate to produce effective antifungal protection. Dendritic cells (DCs) play an important role in initiating and orchestrating antifungal immunity; neutrophils, macrophages and other phagocytes also participate in recognising and eliminating fungal pathogens. Adaptive immunity provides a wide range of effector and regulatory responses against fungal infections. Th1 responses protect against most forms of mycoses but they associate with significant inflammation and limited pathogen persistence. By contrast, Th2 responses enhance persistence of and tolerance to fungal infections thus permitting the generation of long-lasting immunological memory. Although the role of Th17 cytokines in fungal immunity is not fully understood, they can enhance proinflammatory or anti-inflammatory responses or play a regulatory role in fungal immunity all depending on the pathogen, site/phase of infection and host immunostatus. T regulatory cells balance the activities of various Th cell subsets thereby permitting inflammation and protection on the one hand and allowing for tolerance and memory on the other. Here, recent developments in fungal immunity research are reviewed as means of tracing the emergence of a refined paradigm where innate and adaptive responses are viewed in the same light.

Estrogen treatment predisposes to severe and persistent vaginal candidiasis in diabetic mice

“…Estrogen acts on both the fungus and the reproductive tract epithelium of the host to enhance fungal adhesion, hyphal growth, and colonization [2,3]. The immunosuppressive effect of estrogen is also thought to play a significant role in the pathogenesis of VC [9,10]. The indispensable role of estrogen in the induction and maintenance of VC is evidenced by the fact that estrogen-dependent VC animal models are routinely used to study various aspects of the pathogenesis and immunity of VC in mice and rats [11-15].…”

“…With regard to DM, mounting epidemiological evidence suggest that diabetic females are at greater risk of developing VC than non-diabetic counterparts [11,12,14-16] due to glucose abundance [5] and weakened immunity [16] among other possibilities. Weakened or compromised immunity resulting from the pathogenesis or management of various disease states (cancer, AIDS, organ-transplantation) has also been shown to associate with increased risk of VC [10,17,18]. …”

Universal fungal vaccines

“…Lastly, although immunity against fungal pathogens is only beginning to be characterized at the molecular level, 12 it seems that the array of complex mechanisms involved in regulating fungal immunity are prone to failure. Increased risk of pathological inflammation that often associates with fungal immunity is a case in point.…”

“…Approaches to ensure that molecular mechanisms involved in regulating vaccine-related immune responses do not breakdown following immunization have yet to be fully investigated. Development of vaccines that incorporate a means of manipulating the activity of indoleamine 2,3-dioxygenase-1 (IDO), a key immunoregulatory enzyme, 12,13 is an approach that could be further investigated.…”

“…The question of how to make vaccines more consistent so as to induce uniform responses against different pathogens also requires further investigation. Whether engaging Th17 immunity 12,44,55 should be sought irrespective of the pathogen, nature of the vaccine and health status of the host remains an open question.…”