Rat eosinophils stimulate the expansion of Cryptococcus neoformans-specific CD4+ and CD8+ T cells with a T-helper 1 profile

Abstract

Summary Experimental Cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, revealing a strong granulomatous response and a low susceptibility to dissemination. Moreover, it has been shown that eosinophils are components of the inflammatory response to C. neoformans infections. In this in vitro study, we demonstrated that rat peritoneal eosinophils phagocytose opsonized live yeasts of C. neoformans, and that the phenomenon involves the engagement of FcγRII and CD18. Moreover, our results showed that the phagocytosis of opsonized C. neoformans triggers eosinophil activation, as indicated by (i) the up‐regulation of major histocompatibility complex (MHC) class I, MHC class II and costimulatory molecules, and (ii) an increase in interleukin (IL)‐12, tumour necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ) production. However, nitric oxide (NO) and hydrogen peroxide (H2O2) synthesis by eosinophils was down‐regulated after interaction with C. neoformans. Furthermore, this work demonstrated that CD4+ and CD8+ T lymphocytes isolated from spleens of infected rats and cultured with C. neoformans‐pulsed eosinophils proliferate in an MHC class II‐ and class I‐dependent manner, respectively, and produce important amounts of T‐helper 1 (Th1) type cytokines, such as TNF‐α and IFN‐γ, in the absence of T‐helper 2 (Th2) cytokine synthesis. In summary, the present study demonstrates that eosinophils act as fungal antigen‐presenting cells and suggests that C. neoformans‐loaded eosinophils might participate in the adaptive immune response.

Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis

“…Eosinophils have been mentioned before in murine models of cryptococcosis, 10,23,[41][42][43] observed in human cryptococcosis, 44 -46 and described with an emphasis on tissue damage. 41 Although in vitro eosinophils have phagocytosed C. neoformans 23 and presented cryptococcal antigens, 47 in vivo, no evidence for uptake of C. neoformans by eosinophils has been found by others 4 and in this study (data not shown). Herein, we highlight an immunoregulatory role of eosinophils that contribute to IL-4 -dependent immunopathological features during murine pulmonary C. neoformans infection.…”

Humoral Immunity Provides Resident Intestinal Eosinophils Access to Luminal Antigen via Eosinophil-Expressed Low-Affinity Fcγ Receptors

“…Fc receptor repertoires and functions are not directly transposable between mice and humans (47); unlike mouse eosinophils, human peripheral blood eosinophils constitutively express FcγRIIA (21, 48), which, like mouse FcγRIII, is an activating receptor (47). A number of in vitro studies using eosinophils from rodents and human blood demonstrate that exposure of eosinophils to immune complexes or cross-linking eosinophil-expressed Fc gamma receptors elicits eosinophil activation (22), degranulation of cationic granule proteins (21, 25, 49), growth factor (23) and cytokine secretion (50, 51), superoxide production (25), enhanced survival (24), and antigen presenting cell functions to expand both CD4 + and CD8 + lymphocytes (51). Our data shown here now provide a mechanism by which these known Fc gamma receptor-dependent functions may be linked to resident intestinal eosinophils in vivo in secondary immunity.…”

The Intracellular Life ofCryptococcus neoformans

“…Although they are less studied, other types of innate immune cells are found in granulomas and may play a role in defense against cryptococcosis (29). The presence of either excess eosinophils or excess neutrophils is associated with poor control of infection in mice (30, 31), whereas eosinophils might have a beneficial role in rats (32). …”