Modern Lineages of Mycobacterium tuberculosis Exhibit Lineage-Specific Patterns of Growth and Cytokine Induction in Human Monocyte-Derived MacrophagesReportar como inadecuado




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Background

Strains of Mycobacterium tuberculosis vary in virulence. Strains that have caused outbreaks in the United States and United Kingdom have been shown to subvert the innate immune response as a potential immune evasion mechanism. There is, however, little information available as to whether these patterns of immune subversion are features of individual strains or characteristic of broad clonal lineages of M. tuberculosis.

Methods

Strains from two major modern lineages lineage 2 East-Asian and lineage 4 Euro-American circulating in the Western Cape in South Africa as well as a comparator modern lineage lineage 3 CAS-Delhi were identified. We assessed two virulence associated characteristics: mycobacterial growth in liquid broth and monocyte derived macrophages and early pro-inflammatory cytokine induction.

Results

In liquid culture, Lineage 4 strains grew more rapidly and reached higher plateau levels than other strains lineage 4 vs. lineage 2 p = 0.0024; lineage 4 vs. lineage 3 p = 0.0005. Lineage 3 strains were characterized by low and early plateau levels, while lineage 2 strains showed an intermediate growth phenotype. In monocyte-derived macrophages, lineage 2 strains grew faster than lineage 3 strains p<0.01 with lineage 4 strains having an intermediate phenotype. Lineage 2 strains induced the lowest levels of pro-inflammatory TNF and IL-12p40 as compared to other lineages lineage 2: median TNF 362 pg-ml, IL-12p40 91 pg-ml; lineage 3: median TNF 1818 pg-ml, IL-12p40 123 pg-ml; lineage 4: median TNF 1207 pg-ml, IL-12p40 205 pg-ml;. In contrast, lineage 4 strains induced high levels of IL-12p40 and intermediate level of TNF. Lineage 3 strains induced high levels of TNF and intermediate levels of IL-12p40.

Conclusions

Strains of M. tuberculosis from the three major modern strain lineages possess distinct patterns of growth and cytokine induction. Rapid growth and immune subversion may be key characteristics to the success of these strains in different human populations.



Autor: Rajesh Sarkar, Laura Lenders, Katalin A. Wilkinson, Robert J. Wilkinson, Mark P. Nicol

Fuente: http://plos.srce.hr/



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