The Acute Neutrophil Response Mediated by S100 Alarmins during Vaginal Candida Infections Is Independent of the Th17-Pathway

Abstract

Vulvovaginal candidiasis (VVC) caused by Candida albicans affects a significant number of women during their reproductive ages. Clinical observations revealed that a robust vaginal polymorphonuclear neutrophil (PMN) migration occurs in susceptible women, promoting pathological inflammation without affecting fungal burden. Evidence to date in the mouse model suggests that a similar acute PMN migration into the vagina is mediated by chemotactic S100A8 and S100A9 alarmins produced by vaginal epithelial cells in response to Candida. Based on the putative role for the Th17 response in mucosal candidiasis as well as S100 alarmin induction, this study aimed to determine whether the Th17 pathway plays a role in the S100 alarmin-mediated acute inflammation during VVC using the experimental mouse model. For this, IL-23p19−/−, IL-17RA−/− and IL-22−/− mice were intravaginally inoculated with Candida, and vaginal lavage fluids were evaluated for fungal burden, PMN infiltration, the presence of S100 alarmins and inflammatory cytokines and chemokines. Compared to wild-type mice, the cytokine-deficient mice showed comparative levels of vaginal fungal burden and PMN infiltration following inoculation. Likewise, inoculated mice of all strains with substantial PMN infiltration exhibited elevated levels of vaginal S100 alarmins in both vaginal epithelia and secretions in the vaginal lumen. Finally, cytokine analyses of vaginal lavage fluid from inoculated mice revealed equivalent expression profiles irrespective of the Th17 cytokine status or PMN response. These data suggest that the vaginal S100 alarmin response to Candida does not require the cells or cytokines of the Th17 lineage, and therefore, the immunopathogenic inflammatory response during VVC occurs independently of the Th17-pathway.

Nanostructured lipid system as a strategy to improve the anti-Candida albicans activity of Astronium sp.

“…All protocols were approved by the Ethics Committee on the Use of Animals in Research -CEUA School of Pharmaceutical Sciences of Araraquara -UNESP (protocol number 34/2013 34 using a micropipette with disposable tips. On days 2, 6, and 10 after the infection, the vaginal load of C. albicans was evaluated through vaginal lavage with 0.1 mL of PBS, and the fungal count was determined by the CFU assay on sabouraud dextrose agar (SDA).…”

Immune Response, Detection of IgE and PGE2 during Vaginal Candidiasis in Mice

“…2) prior to the infection time, however in some infection times detectable changes in the cellular pattern of the sub mucosal layer were observed, possibly due to lack of fungi invasion in deeper structures, which could lead to more effective and diversified cellular immune response (Black et al, 1998;de Bernardis et al, 2000). Yano et al (2012) demonstrated an important polymorphonuclear role in the symptomatic VVC infection establishment, which seems to be related to alarmins production by the vaginal epithelial cells. These molecules are able to attract PMN and contribute to the acute VVC symptoms.…”

“…VVC is an opportunistic infection that affects 75% of women during their reproductive life and about 5% of them will develop Recurrent Vulvovaginal Candidiasis (RVVC) (Fidel et al, 1995;Carrara et al, 2010;Harriott et al, 2010;Yano et al, 2012). The mechanism of defense used by the host against this fungus is related to an activity of innate and adaptive immune response (Yano et al, 2012).…”

“…The mechanism of defense used by the host against this fungus is related to an activity of innate and adaptive immune response (Yano et al, 2012). However, the exact knowledge on how the putative immune system mechanisms of the female genital treatment react against this yeast is still unclear.…”

Overexpression of Candida albicans Secreted Aspartyl Proteinase 2 or 5 Is Not Sufficient for Exacerbation of Immunopathology in a Murine Model of Vaginitis

“…Surprisingly, SAP overexpression strains did not recruit more neutrophils than their isogenic empty vector control did. We previously identified the pleiotropic innate inflammatory cytokine IL-1␤ as a relevant biomarker of vaginal immunopathology and known effector of inflammasome activa- tion, a crucial host signaling pathway activated during murine VVC (4,6,(22)(23)(24)(25). Importantly, recombinant SAPs have also been demonstrated to activate the inflammasome and to liberate IL-1␤ in the vaginal epithelium (16,26,27).…”