Crosstalk between leukocytes triggers differential immune responses against < i > Salmonella enterica < /i > serovars Typhi and Paratyphi

by Rosangela Salerno-Goncalves, Darpan Kayastha, Alessio Fasano, Myron M. Levine, Marcelo B. Sztein Enteric fevers, caused by theSalmonella enterica serovars Typhi (ST), Paratyphi A (PA) and Paratyphi B (PB), are life-threatening illnesses exhibiting very similar clinical symptoms but with distinct epidemiologies, geographical distributions and susceptibilities to antimicrobial treatment. Nevertheless, the mechanisms by which the host recognizes pathogens with high levels of homology, such as these bacterial serovars, remain poorly understood. Using a three-dimensional organotypic model of the human intestinal mucosa and PA, PB, and ST, we observed significant differences in the secretion patterns of pro-inflammatory cytokines and chemokines elicited by these serovars. These cytokines/chemokines were likely to be co-regulated and influenced the function of epithelial cells, such as the production of IL-8. We also found differing levels of polymorphonuclear leukocyte (PMN) migration among various infection conditions that either included or excluded lymphocytes and macrophages (M ϕ), strongly suggesting feedback mechanisms among these cells. Blocking experiments showed that IL-1β, IL-6, IL-8, TNF-α and CCL3 cytokines were involved in the differential regulation of migration patterns. We conclude that the crosstalk among the lymphocytes, Mϕ, PMN and epithelial cells is cy tokine/chemokine-dependent and bacterial-serotype specific, and plays a pivotal role in orchestrating ...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research