Brucella abortus Induces the Premature Death of Human Neutrophils through the Action of Its Lipopolysaccharide

 

সংরক্ষণ করুন:
গ্রন্থ-পঞ্জীর বিবরন
লেখক: Barquero Calvo, Elías, Mora Cartín, Ricardo, Arce Gorvel, Vilma, de Diego, Juana L., Chacón Díaz, Carlos, Chaves Olarte, Esteban, Guzmán Verri, Caterina, Buret, Andre G., Gorvel, Jean Pierre, Moreno Robles, Edgardo
বিন্যাস: artículo original
প্রকাশনার তারিখ:2015
বিবরন:Most bacterial infections induce the activation of polymorphonuclear neutrophils (PMNs), enhance their microbicidal function, and promote the survival of these leukocytes for protracted periods of time. Brucella abortus is a stealthy pathogen that evades innate immunity, barely activates PMNs, and resists the killing mechanisms of these phagocytes. Intriguing clinical signs observed during brucellosis are the low numbers of Brucella infected PMNs in the target organs and neutropenia in a proportion of the patients; features that deserve further attention. Here we demonstrate that B. abortus prematurely kills human PMNs in a dose-dependent and cell-specific manner. Death of PMNs is concomitant with the intracellular Brucella lipopolysaccharide (Br-LPS) release within vacuoles. This molecule and its lipid A reproduce the premature cell death of PMNs, a phenomenon associated to the low production of proinflammatory cytokines. Blocking of CD14 but not TLR4 prevents the Br-LPS-induced cell death. The PMNs cell death departs from necrosis, NETosis and classical apoptosis. The mechanism of PMN cell death is linked to the activation of NADPH-oxidase and a modest but steadily increase of ROS mediators. These effectors generate DNA damage, recruitments of check point kinase 1, caspases 5 and to minor extent of caspase 4, RIP1 and Ca++ release. The production of IL-1β by PMNs was barely stimulated by B. abortus infection or Br-LPS treatment. Likewise, inhibition of caspase 1 did not hamper the Br-LPS induced PMN cell death, suggesting that the inflammasome pathway was not involved. Although activation of caspases 8 and 9 was observed, they did not seem to participate in the initial triggering mechanisms, since inhibition of these caspases scarcely blocked PMN cell death. These findings suggest a mechanism for neutropenia in chronic brucellosis and reveal a novel Brucella-host cross-talk through which B. abortus is able to hinder the innate function of PMN.
দেশ:Kérwá
প্রতিষ্ঠান:Universidad de Costa Rica
Repositorio:Kérwá
OAI Identifier:oai:https://www.kerwa.ucr.ac.cr:10669/76878
অনলাইন ব্যবহার করুন:https://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1004853
https://hdl.handle.net/10669/76878
Access Level:acceso abierto
মুখ্য শব্দ:Bacterial
PMNs
Neutrophils
579.33 Bastoncitos y cocos aeróbicos gram-negativos