Alfonseca-Silva Edgar, Hernández-Pando Rogelio, Gutiérrez-Pabello José A
Laboratorio de Investigación en Tuberculosis Bovina, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Coyoacán, México, D.F. 04510, Mexico.
Patología Experimental, Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Vasco de Quiroga 15, Tlalpan, México, D.F. 14000, Mexico.
Vet Immunol Immunopathol. 2016 Aug;176:34-43. doi: 10.1016/j.vetimm.2016.02.015. Epub 2016 Feb 27.
Mycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular bacterium that normally persists inside host macrophages. However, the influence of bacterial virulence and host resistance on the final outcome in this interaction is not well known. In this study, we infected macrophages isolated from natural disease resistant (R) and susceptible (S) cattle donors with M. bovis strains characterized as attenuated and virulent to assess pro-inflammatory cytokine (TNFα, IL-12, IL-18, IL-1β, IL-6), chemokine (MCP-1, MCP-2, MIP-1), macrophage receptor (MSR1, TLR2, TLR4, MMR) and iNOS mRNA expression levels. Our findings identified a pro-inflammatory gene expression profile as a common feature after M. bovis infection regardless of bacterial virulence, however in S macrophages a superior expression was induced by the attenuated strain, whereas in R macrophages it was accomplished by the virulent M. bovis. A macrophage pro-inflammatory profile is intended to control M. bovis intracellular growth; however the host resistant phenotype plays a determinant role in it, since R macrophages had better intracellular bacterial control than S cells.
牛分枝杆菌是牛结核病的病原体，是一种细胞内细菌，通常在宿主巨噬细胞内持续存在。然而，细菌毒力和宿主抵抗力对这种相互作用最终结果的影响尚不清楚。在本研究中，我们用被鉴定为减毒和有毒力的牛分枝杆菌菌株感染从天然抗病（R）和易感（S）牛供体分离的巨噬细胞，以评估促炎细胞因子（TNFα、IL-12、IL-18、IL-1β、IL-6）、趋化因子（MCP-1、MCP-2、MIP-1）、巨噬细胞受体（MSR1、TLR2、TLR4、MMR）和诱导型一氧化氮合酶（iNOS）的mRNA表达水平。我们的研究结果表明，无论细菌毒力如何，促炎基因表达谱是牛分枝杆菌感染后的一个共同特征，然而在S巨噬细胞中，减毒株诱导了更高的表达，而在R巨噬细胞中，有毒力的牛分枝杆菌实现了更高的表达。巨噬细胞促炎谱旨在控制牛分枝杆菌的细胞内生长；然而，宿主抗性表型在其中起决定性作用，因为R巨噬细胞比S细胞对细胞内细菌有更好的控制。
