Altered, but not diminished specific T cell response in chronic mucocutaneous candidiasis patients

Abstract

Patients suffering from chronic mucocutaneous infections with the yeast Candida albicans (CMC) are discussed to have an underlying primary cellular immunodeficiency. In order to characterise cellular immunity in CMC patients, we analysed chemotaxis and myeloperoxidase (MPO) releases of neutrophils and T cell proliferation and cytokine production to Candida albicans. Patients with chronic mucocutaneous candidiasis (n = 4) and healthy volunteers of same sex and similar age (n = 14) were enrolled into the study. Neutrophil chemotaxis was assessed by transwell migration assay, and MPO release by ELISA. T cell proliferation capacity was investigated by thymidine incorporation and cytokine secretion in supernatants by ELISA. Neither neutrophil migration nor MPO release differed between CMC patients and healthy controls. The relative lymphocyte stimulation index (SI Candida/SI PHA) was heterogenous, but overall it was higher in CMC patients compared to controls. However, Candida-specific IFN-gamma production was significantly reduced in CMC patients. Notably, Candida-specific T cell IL-10 production was markedly higher in CMC patients. The inability to clear the yeast Candida albicans in our CMC patients does not seem to be due to an impaired neutrophil function or reduced antigen specific proliferation of lymphocytes. In fact, our patients tended to proliferate stronger to Candida antigen relative to PHA than healthy controls. However, the impaired Th1 cytokine production with an enhanced IL-10 production could play an important role in the pathogenesis of chronic mucocutaneous Candida infections.

Chronic mucocutaneous candidiasis and congenital susceptibility to Candida

“…A wide range of different immunologic abnormalities in T cells of CMC patients has been described [7, [65][66][67][68]. In recent years, however, Th17 cells, a subset of T helper cells producing IL-17A/F and IL-22, moved to the centre of attention and have been shown to play a major role in the defence against C. albicans.…”

Neutrophil Myeloperoxidase: Soldier and Statesman

“…This enzyme, discovered over 40 years ago, was long believed to be a key component of the phagocyte oxygen-dependent intracellular microbicidal system, and thus to play an important part in the effector phase of innate immune responses (Klebanoff 1967). However, the limited immunodeficiency associated with lack of MPO in mouse and human models (Aratani et al 2000(Aratani et al , 2002Eyerich et al 2007;Lanza 1998;Parry et al 1981) has challenged this paradigm. Two recent reviews summarize many of the different possible additional functions suggested for MPO (Arnhold and Flemmig 2010;Van der Veen et al 2009).…”

Immunological and histopathological characterization of cutaneous candidiasis

“…*P,0.05. Eyerich et al, 2007Eyerich et al, , 2008, special attention was given to the cytokines produced by these cells in this study.…”

“…T-cell subtypes. Numerous studies have described altered cytokine production with reduced production of type 1 cytokines, such as IFN-c, IL-12 and IL-2, and increased secretion of IL-10 or IL-4 and IL-5 (Kobrynski et al, 1996;Lilic et al, 2003;van der Graaf et al, 2003;Eyerich et al, 2007). In T-helper 1 (Th1) responses, IL-12 and IFN-c production are essential for controlling C. albicans infections, whereas Th2 cytokines are associated with increased susceptibility to infection (Cenci et al, 1998;Romani, 2004).…”