Cytokine Gene Polymorphisms and the Outcome of Invasive Candidiasis: A Prospective Cohort Study

Invasive candidiasis is a pervasive nosocomial infection. Although some patients may experience only transient fungemia, others develop complications including endocarditis, abscesses, and chronic-disseminated candidiasis. Persistent fungemia is an increasingly recognized complication of candidemia, which occurs in 8%–15% of candidemia patients. Few studies have provided an explanation for these differential outcomes, although immune response to infection, comorbidities, and pharmacologic therapy have all been suggested to contribute to patient outcomes [1]. Both innate and adaptive immune mechanisms are important for host defense against Candida species [2]. The innate immune system provides the first line of defense against fungal pathogens by phagocytosis and killing of invading pathogens, as well as through activation of adaptive immunity through antigen presentation and secretion of proinflammatory cytokines [3]. Adaptive fungal immunity stimulates host responses to pathogens via protective cellular T-helper 1 (Th1) cytokines, such as interferon-γ (IFN-γ), and humoral Th2 responses that may have maladaptive antiinflammatory effects by the release of interleukin (IL)–4 and IL-10. The interplay between Th1 and Th2 responses to Candida infection is complex but critical for the response to this pathogen. Previous studies have demonstrated that vigorous Th1-type responses are essential for eradication of Candida [4, 5]. In contrast, Th2-type responses to Candida may lead to downregulation of proinflammatory cytokines, thereby terminating the protective response to infection [6]. Genetic factors are known to have an important impact on susceptibility to infections [7]. Although much has been learned about the immune mechanisms that determine an effective host defense against Candida, very little is known about the role played by single-nucleotide polymorphisms (SNPs) of genes comprising the cytokine network for susceptibility to systemic candidiasis. This study was undertaken to investigate the role of polymorphisms in the main cytokine genes for the susceptibility to Candida infection and to assess whether there is any association with the subsequent clinical outcome.