Reduced in vivo Cytotoxicity and Increased Mycobacterial Burden Are Associated with Virulent Mycobacterium tuberculosis Strains During Lung Infection

Abstract

Cytotoxic cellular responses are crucial for clearing intracellular pathogens and generating host resistance. Experimental pulmonary tuberculosis is associated with an early delay in T cell responses and with elevated lung bacterial burden during chronic infection. In this study we quantified the in vivo cytotoxicity and the mycobacterial burden from two pertinent tissues in groups of mice infected each with a mycobacterial strain of different virulence. None of the strains induced cytotoxic responses during early (day 14) infection. Interestingly, at 21 and 60 days post-infection, Mycobacterium canettii (lowest virulence) triggered the strongest in vivo cytotoxicity both in lungs and mediastinal lymph nodes. In contrast, Mycobacterium tuberculosis H37Rv (intermediate virulence) and Beijing strains (highest virulence) induced lower cytotoxic responses, and exhibited high bacterial growth, especially in lungs. These in vivo data suggest that virulence of Mycobacterium strains are somehow associated with subverting cytotoxic responses, thus contributing to early bacterial replication and subsequent persistence in the lungs.

• virulent mycobacterium strains
• in vivo cytotoxicity
• M. canettii
• M. Beijing
• M. H37Rv.

ACKNOWLEDGMENTS

We thank Dr. Rafi Ahmed for kindly helping us to establish and adapt the in vivo cytotoxicity assay and Dr. M. Zaidi for critical reading of the manuscript. L Quintero-Macías, E Valderrabano-Ortiz, R Munguia-Fuentes and A Silva-Sanchez received fellowships from the National Council for Science and Technology, Conacyt. Partial support was from Conacyt project 47442-M, and from the European Commission 6^th framework programme on research technological development demonstration (project no. 037919). A. Silva-Sanchez, R. Hernandez-Pando and L Flores-Romo are members of the National System of Researchers of Mexico, SNI.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.