Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

Abstract

eThe genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-␣) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-␣ and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue.

Natural history ofMycobacterium aviumcomplex lung disease in untreated patients with stable course

“…This is supported by the fact that an elevation in inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate was significantly associated with MAC-LD progression, further impacting the degree of sputum conversion and MAC-specific mortality [7,9,20]. It has been found that many pro-or anti-inflammatory cytokines are activated to varying degrees in severe, advanced MAC infection [21][22][23].…”

Type II Interferon Promotes Differentiation of Myeloid-Biased Hematopoietic Stem Cells

“…To determine whether selection of My‐HSCs by IFNγ signaling occurs during infection in vivo, we utilized M. avium infection to elicit an IFNγ‐mediated immune response in mice . Notably, the M. avium ‐infected animals showed a specific depletion in the proportion and total number of HSCs in the lower part of the SP distribution, characteristic of myeloid‐biased HSCs.…”

Molecular Identification of Mycobacterium Species of Public Health Importance in Cattle in Zimbabwe by 16S rRNA Gene Sequencing

“…Humans are exposed to Mycobacterium from domestic animals through contami-nated foodstuffs or by direct contact with the animals and their products [ 7 , 8 ]. Several species of environmental Myco-bacterium are now known to be of public health importance since they are pathogenic to humans especially those with underlying medical conditions such as being immunocom-promised [ 9 - 11 ]. Rapid detection and identifi-cation of environmental mycobacteria at species level is therefore critical if infections in humans and animals are to be controlled.…”