The effects of Cryptococcus neoformans-secreted antigens on tumor necrosis factor-α-induced intercellular adhesion molecule-1 expression on human lung epithelial cells

Abstract

Since primary infection with Cryptococcus neoformans usually occurs in the lungs, and since pulmonary cryptococcosis involves interactions between yeasts and alveolar epithelial cells, we have begun to study the effects of C. neoformans and its secreted antigens (SA) on epithelial reactions potentially associated with localized inflammation. We report here that SAs from encapsulated and acapsular strains of C. neoformans caused significant reductions in tumor necrosis factor-alpha (TNF-alpha)-induced intercellular adhesion molecule-1 (ICAM-1) expression on A549 lung epithelial cells in culture. We also present evidence that the reduction in ICAM-1 expression was not associated with SA-induced shedding of this adhesion molecule.

Cryptococcus–Epithelial Interactions

“…The influence of cryptococci on epithelial cell ligand expression and how this might influence immune cell recruitment has also been investigated. Intercellular adhesion molecule-1 (ICAM-1) expression on epithelial cells can be increased via TNFα [ 39 ]. ICAM-1 can help the attachment of monocytes expressing CR3 ligand, or neutrophils, B cells and T-cells that express LFA-1 ligand, helping recruitment and perhaps keeping cells there until local infection is cleared.…”

“…Rather than looking at direct adherence of cryptococci to epithelial cells this time Merkel et al, investigated the effect of cryptococcal secreted products on epithelial cells. It was discovered that the heat stable secreted products of C. neoformans were able to interfere with TNF-α orchestrated ICAM-1 expression [ 39 ]. The authors propose that this is not cryptococcal components inducing ICAM-1 shedding, but is more likely to be due to blocking the TNF-α receptor or causing loss of the TNF-α receptor.…”

The still obscure attributes of cryptococcal glucuronoxylomannan

“…The latter include human type II alveolar cells (A549 cell lineage) [26], immortalized bronchial epithelial cells and primary normal human bronchial epithelium [28]. As detailed below, the outcome of the interaction of C. neoformans with lung epithelial cells includes the induction of the chemokines IL-8 and CXCL1 [28,29], production of the transcription factor CEBP/β[28] and significant reductions in tumor necrosis factor-alpha (TNF-alpha)-induced intercellular adhesion molecule-1 (ICAM-1) expression [30]. Therefore, it is reasonable to expect that epithelial cells contribute to the initial stages of pulmonary host response to C. neoformans .…”