%0 Journal Article
%T An Elucidation of Neutrophil Functions against Mycobacterium tuberculosis Infection
%A Devin Morris
%A Thien Nguyen
%A John Kim
%A Christine Kassissa
%A Melissa Khurasany
%A Jennifer Luong
%A Sarah Kasko
%A Shalin Pandya
%A Michael Chu
%A Po-Ting Chi
%A Judy Ly
%A Minette Lagman
%A Vishwanath Venketaraman
%J Journal of Immunology Research
%D 2013
%R 10.1155/2013/959650
%X We characterized the functions of neutrophils in response to Mycobacterium tuberculosis (M. tb) infection, with particular reference to glutathione (GSH). We examined the effects of GSH in improving the ability of neutrophils to control intracellular M. tb infection. Our findings indicate that increasing the intracellular levels of GSH with a liposomal formulation of GSH (L-GSH) resulted in reduction in the levels of free radicals and increased acidification of M. tb containing phagosomes leading to the inhibition in the growth of M. tb. This inhibitory mechanism is dependent on the presence of TNF-¦Á and IL-6. Our studies demonstrate a novel regulatory mechanism adapted by the neutrophils to control M. tb infection. 1. Introduction M. tb, a causative agent for tuberculosis (TB), is known to be a highly successful intracellular pathogen and is estimated to be harbored in one third of the world¡¯s population [1]. Left untreated TB is known to have a 70% mortality rate [2]. Increasing drug resistance strains of M. tb and poor precautionary measurements for containing the spread, especially in ¡°high burden¡± countries, have kept the disease from global eradication [1]. M. tb infection is mostly confined to lungs and can be transmitted by inhalation of droplets from individuals with active TB. M. tb has the ability to evade the host killing mechanisms and can successfully persist inside the phagocytic cells. Specifically, M. tb is capable of surviving within the host cells by preventing the fusion of the phagosomes containing bacteria with lysosomes, thereby avoiding exposure to the toxic lysosomal hydrolases [3]. The terminally differentiated polymorphonuclear leukocytes (PMN) or neutrophils are essential component of the human innate immune system and act as a first-line defense against invading microorganisms. Neutrophils are major inhabitants of the white blood cell population (WBC) since they constitute ~70% of the total WBC population [4]. Neutrophils form the bulk of early recruited leukocyte population that mediate and elicit immune responses against M. tb [4]. Neutrophils, after encountering the mycobacteria, exhibit innate immune responses such as phagocytosis which in turn triggers signaling events resulting in secretion of cytokines such as TNF-¦Á and IL-1 that mediate early inflammatory responses [4¨C6]. The tripeptide, glutathione (GSH), protects all cells against oxidizing agents, free radicals, and reactive oxygen intermediates (ROI), either directly or through enzymatic action of GSH peroxidases and GSH-transferases [7, 8]. GSH is also important
%U http://www.hindawi.com/journals/jir/2013/959650/