Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients

Abstract

This study was funded by the UC Merced Blum Center (to D.M.O. and K.K.H.), Valley Children's Healthcare (to F.

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

“…Studies are showing the involvement of CCR5 in some fungal diseases, including Aspergillus fumigatus ‐induced asthma in mice (Schuh, Blease, Brühl, Mack, & Hogaboam, 2003; Schuh, Blease, & Hogaboam, 2002), and infections by Candida albicans (Kim et al, 2005), Paracoccidioides brasiliensis (Moreira et al, 2008), Histoplasma capsulatum in mice (Kroetz & Deepe, 2010, 2011, 2012) and Coccidioides (Davini et al, 2018). Due to the limited number of studies that have addressed CCR5 in the context of human fungal infections, it is not yet possible to establish the real importance of this receptor in the clinical course of these diseases.…”

“…Pieces of evidence point to a role of CCR5 in the mediation of recruitment and action of regulatory T (Treg) cells in fungal (Davini et al, 2018; Kroetz & Deepe, 2010), bacterial (Ahmed et al, 2018), parasitic (Romano et al, 2016; Souza et al, 2011; Yurchenko et al, 2006) and viral (Kim et al, 2016) infections. CCR5 + Treg cells have immunosuppressive activity (Soler et al, 2013) and CCR5 signalling mediates the recruitment of Treg cells to inflammation sites, thus modulating inflammatory responses by inducing a Treg‐mediated immunosuppressive environment (Dobaczewski, Xia, Bujak, Gonzalez‐Quesada, & Frangogiannis, 2010; Doodes et al, 2009; Li et al, 2017; Velasco‐Velázquez, Xolalpa, & Pestell, 2014; Wildenberg et al, 2008).…”

Host Response to Coccidioides Infection: Fungal Immunity

“…In a 1:1 neutrophil to Coccidioides endospore interaction, human neutrophils readily phagocytose Coccidioides endospores and exhibit partial phagocytosis of larger spherules, coined "frustrated phagocytosis" (Lee et al, 2015). Neutrophils from healthy patients and chronic coccidioidomycosis patients exhibit similar neutrophil phagocytosis capabilities; however, high neutrophil presence is associated with chronic Coccidioides infection (Lee et al, 2015;Davini et al, 2018). This suggests that expanded neutrophil presence is detrimental for Coccidioides clearance perhaps due to their persistence into later stages of infection that may preclude other more effective responses (Davini et al, 2018).…”

“…Neutrophils from healthy patients and chronic coccidioidomycosis patients exhibit similar neutrophil phagocytosis capabilities; however, high neutrophil presence is associated with chronic Coccidioides infection (Lee et al, 2015;Davini et al, 2018). This suggests that expanded neutrophil presence is detrimental for Coccidioides clearance perhaps due to their persistence into later stages of infection that may preclude other more effective responses (Davini et al, 2018). This in combination with neutrophil inability to fully phagocytose large endospores may make neutrophils ineffective, allowing prolonged fungal infection.…”

Host–Pathogen Interactions in Coccidioidomycosis: Prognostic Clues and Opportunities for Novel Therapies

“…Thus, induced regulatory T cells and Th17 cells form a balance of protective and repressive immunity based on the inflammatory context at the time of priming. This balance seems to be clinically important in determining dissemination of coccidioidal infection in humans, 67 although the data are limited, and it is unclear if regulatory T cells are purely suppressive of protective immunity. The complex relationship between Th17 cells and regulatory T cells offers some evidence that these cell types can, in fact, work cooperatively to promote adaptive immunity toward fungi.…”