Microparticles induce variable levels of activation in macrophages infected with Mycobacterium tuberculosis

作者：Yadav Awadh B; Muttil Pavan; Singh Amit K; Verma Rahul K; Mohan Mradul; Agrawal Atul K; Verma Ajay S; Sinha Sudhir K; Misra Amit^*

来源：Tuberculosis, 2010, 90(3): 188-196.

DOI：10.1016/j.tube.2010.03.001

• Macrophage
• Cytokines
• Nitric oxide
• Apoptosis
• Microspheres

Activation of human macrophages infected with Mycobacterium tuberculosis was investigated following exposure to microparticles (MP) possessing high anti-tubercular efficacy in mice. A small set of innate responses (cytokine profiles, NO production, Annexin-V staining and caspase-8, caspase-9 and caspase-3 activities) of differentiated THP-1 cells or human monocyte-derived macrophages infected 1: 10 in vitro were compared. Cytokines of THP-1 macrophages were comparable in trends, but not in magnitude, with five human genotypes studied. MP reversed suppression of tumor necrosis factor induced by infection, and transiently upregulated gamma-interferon. Drug-free MP surprisingly induced gamma-interferon, but not tumor necrosis factor. Primary cells responded to MP, regardless of drug content, by upregulation of NO; but THP-1 cells did not respond to drug-free MP. About 19% of infected cells exposed to MP underwent apoptosis compared to similar to 11% cells treated otherwise. Cell death induced by drug-free MP was caspase independent. Intracellular bacterial survival varied between individuals. Untreated infection resulted in survival of 900 +/- 141 cfu; exposure to soluble drugs, drug-containing and blank microparticles respectively, reduced CFU counts to < 10, < 10 and 102 +/- 139. These observations indicate that despite variations in magnitude between cells from different sources, innate responses conducive to killing intracellular bacteria were evoked by inhalable MP.

• 出版日期2010-5