Intravenous Immunoglobulin Therapy Eliminates Candida albicans and Maintains Intestinal Homeostasis in a Murine Model of Dextran Sulfate Sodium-Induced Colitis.

Rogatien Charlet,Samir Jawhara,Daniel Poulain,Jagadeesh Bayry,Boualem Sendid,Srini Kaveri

doi:10.3390/ijms20061473

Abstract

Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effects and has been employed successfully in autoimmune and inflammatory diseases. The role of IVIg therapy in the modulation of intestinal inflammation and fungal elimination has not been yet investigated. We studied IVIg therapy in a murine model of dextran sulfate sodium (DSS)-induced colitis. Mice received a single oral inoculum of Candida albicans and were exposed to DSS treatment for 2 weeks to induce colitis. All mice received daily IVIg therapy starting on day 1 for 7 days. IVIg therapy not only prevented a loss of body weight caused by the development of colitis but also reduced the severity of intestinal inflammation, as determined by clinical and histological scores. IVIg treatment significantly reduced the Escherichia coli, Enterococcus faecalis, and C. albicans populations in mice. The beneficial effects of IVIg were associated with the suppression of inflammatory cytokine interleukin (IL)-6 and enhancement of IL-10 in the gut. IVIg therapy also led to an increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), while toll-like receptor 4 (TLR-4) expression was reduced. IVIg treatment reduces intestinal inflammation in mice and eliminates C. albicans overgrowth from the gut in association with down-regulation of pro-inflammatory mediators combined with up-regulation of anti-inflammatory cytokines.

Highlights

Candida albicans infections continue to be a serious clinical problem in terms of their high morbidity and mortality [1,2]
In order to analyze the efficiency of Intravenous immunoglobulin (IVIg) in the modulation of intestinal inflammation, mice received 2% dextran sulfate sodium (DSS) for 2 weeks in drinking water to promote the development of colitis
IVIg (Sandoglobulin) was administered via intraperitoneal injection (0.8 g/kg/day for 7 days) to mice treated with DSS and challenged with C. albicans

Summary

Introduction

Candida albicans infections continue to be a serious clinical problem in terms of their high morbidity and mortality [1,2]. Clinical and experimental studies have shown that C. albicans infections can generate anti-glycan antibodies known as ASCA (anti-Saccharomyces cerevisiae mannan antibodies) [4] These anti-fungal glycan antibodies were initially described as serological markers of Crohn’s disease (CD), but subsequent studies have established that they can be generated during Candida infection, suggesting a link between CD gut dysbiosis and endogenous opportunistic fungal species [5,6]. IVIg therapy led to an increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), while toll-like receptor 4 (TLR-4) expression was reduced. These data provide experimental evidence for the therapeutic utility of IVIg in IBD

Results

Animals

Assessment of Clinical and Histological Scores

Real-Time mRNA Quantification of Innate Immune Receptors

Quantification of Cytokines

Statistical Analysis