Analysis of the antimicrobial responses of primary phagocytes of the goldfish (Carassius auratus L.) against Mycobacterium marinum

作者：Grayfer Leon; Hodgkinson Jordan W; Belosevic Miodrag^*

来源：Developmental and Comparative Immunology, 2011, 35(11): 1146-1158.

DOI：10.1016/j.dci.2011.04.007

• Mycobacterium
• Macrophage
• Immune-evasion
• Antimicrobial-response
• Fish
• Cytokine

The slow growth rate of Mycobacterium spp. that infect humans coupled with a lack of reliable in vitro infection model systems has hindered the progress of research in host cell-mycobacteria interactions. Recent studies have utilized the relatively fast growing Mycobacterium marinum to examine the host-pathogen interface in natural fish hosts. Here we describe the use of primary goldfish monocyte and mature macrophage cultures to investigate the immune cell-M. marinum interactions. Live and heat-killed M. marinum abrogated the recombinant goldfish (rg)TNF alpha 2 and rgIFN gamma-induced monocyte reactive oxygen production. Live but not heat-killed M. marinum also ablated rgIFN gamma rel and rg-TNF alpha 2 induced macrophage nitric oxide production. M. marinum induced significant changes in gene expression of select NADPH oxidase components and inflammatory cytokine receptors and up-regulated the expression of immunosuppressive genes IL-10. TGF beta 1 and SOCS-3. The exposure of monocytes and mature macrophages to M. marinum caused an increase in the mRNA levels of several pro-inflammatory genes. Stimulation of monocytes and macrophages with rgTNF alpha 2, rgIFN gamma, or rgIFN gamma rel reduced the survival of intracellular mycobacteria. The characterization of the interaction between M. marinum and natural host-derived primary phagocyte cultures will enable future studies on the host-pathogen interactions in mycobacterial infections.

• 出版日期2011-11