Regulation of Host Chemokine Response by the Pathogenic Type III Secretion System pp. 111-121
Authors: Elizabeth Hong-Geller, Kristy L. Nowak-Lovato, Sofiya N. Micheva-Viteva, Sabine A. Lauer, Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico
Abstract: Human pathogens have evolved sophisticated mechanisms by which to attack the host immune system. One such mechanism is the Type III secretion system (TTSS), a ―syringe-like‖ needle complex that injects virulence proteins, or effector proteins, into the host cell. Subsequent effector interactions with multiple host protein targets lead to inhibition of phagocytosis, regulation of host gene expression, and modulation of the overall host inflammatory response, thus enabling pathogen survival and colonization of the host. TTSSs have been found in over a dozen Gram-negative animal and plant pathogens, underscoring the conservation of this virulence mechanism as an effective strategy for host infection. In the host, chemokines, or chemotactic cytokines, have emerged as central regulatory molecules, forming chemoattractant gradients that direct the migration of neutrophils and macrophages to sites of infection. In multiple studies, chemokine mRNA and protein expression levels have been shown to be regulated in response to host infection by TTSS pathogens, implicating TTSS effector proteins in activation of chemokine function.