Journal Article

Crosstalk between leukocytes triggers differential immune responses against Salmonella enterica serovars Typhi and Paratyphi

Kayastha, Darpan, Levine, Myron M., Sztein, Marcelo B., Fasano, Alessio, Salerno-Goncalves, Rosangela

2019

Overview

Enteric fevers, caused by the Salmonella 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 (Mϕ), 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 cytokine/chemokine-dependent and bacterial-serotype specific, and plays a pivotal role in orchestrating the functional efficiency of the innate cells and migratory characteristics of the leukocytes.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Biology and Life Sciences / CCL3 protein / Cell Communication / Cell Movement / Cells / Chemokines / Crosstalk / Cytokines / Cytokines - analysis / Disease / Epidemiology / Epithelial cells / Epithelial Cells - immunology / Fever / Funding / Geographical distribution / Histopathology / Homology / Host-bacteria relationships / Humans / IL-1β / Illnesses / Immune response / Infections / Inflammation / Interleukin 6 / Interleukin 8 / Intestinal Mucosa - immunology / Intestine / Leukocyte migration / Leukocytes / Leukocytes (polymorphonuclear) / Leukocytes - immunology / Lymphocytes / Lymphocytes - immunology / Macrophages / Macrophages - immunology / Medicine / Medicine and Health Sciences / Models, Theoretical / Mucosa / Neutrophils / Organ Culture Techniques / Pathogens / Pathology / Pediatrics / Physiological aspects / Public health / Research and Analysis Methods / Salmonella / Salmonella enterica / Salmonella paratyphi A - immunology / Salmonella paratyphi B - immunology / Salmonella typhi - immunology / Secretion / Symptoms / Three dimensional models / Tropical diseases / Tumor necrosis factor-α / Typhoid / Typhoid Fever - immunology / Vaccines / Varieties