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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02479

Disparate tuberculosis disease development in macaque species is associated with innate immunity

 Karin Dijkman1*,  Claudia C. Sombroek1, Richard A. Vervenne1,  Charelle Boot1, Sam O. Hofman1, Krista E. van Meijgaarden2,  Tom H. Ottenhoff2, Clemens H. Kocken1,  Krista G. Haanstra1,  Michel P. Vierboom1 and  Frank A. Verreck1
  • 1TB research group, department of Parasitology, Biomedical Primate Research Centre, Netherlands
  • 2Department of Infectious Diseases, Leiden University Medical Center, Netherlands

While tuberculosis continues to afflict mankind, the immunological mechanisms underlying TB disease development are still incompletely understood. Advanced preclinical models for TB research include both rhesus and cynomolgus macaques (Macaca mulatta and Macaca fascicularis, respectively), with rhesus typically being more susceptible to acute progressive TB disease than cynomolgus macaques. To determine which immune mechanisms are responsible for this dissimilar disease development, we profiled a broad range of innate and adaptive responses, both local and peripheral, following experimental pulmonary Mtb infection of both species. While T-cell and antibody responses appeared indistinguishable, we identified anti-inflammatory skewing of peripheral monocytes in rhesus and a more prominent local pro-inflammatory cytokine release profile in cynomolgus macaques associated with divergent TB disease outcome. Importantly, these differences were detectable both before and early after infection. This work shows that inflammatory and innate immune status prior to and at early stages after infection, critically affects outcome of TB infection.

Keywords: Tuberculosis, innate immunity, non-human primates, Experimental models of disease, pulmonary immunology

Received: 30 Jul 2019; Accepted: 04 Oct 2019.

Copyright: © 2019 Dijkman, Sombroek, Vervenne, Boot, Hofman, van Meijgaarden, Ottenhoff, Kocken, Haanstra, Vierboom and Verreck. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Karin Dijkman, Biomedical Primate Research Centre, TB research group, department of Parasitology, Rijswijk, Netherlands, dijkman@bprc.nl