Myeloid HIF-1α regulates pulmonary inflammation during experimental Mycobacterium tuberculosis infection
Resende, Ferreira, Barbosa, Cardoso, Sousa, Saraiva, Castro, Appelberg, Torrado (2020) Myeloid HIF-1α regulates pulmonary inflammation during experimental Mycobacterium tuberculosis infection Immunology (IF: 6.4) 159(1) 121-129
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Abstract
The transcription factor hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulator of the response and function of myeloid cells in hypoxic and inflammatory microenvironments. To define the role of HIF-1α in tuberculosis, the progression of aerosol Mycobacterium tuberculosis infection was analysed in mice deficient in HIF-1α in the myeloid lineage (mHIF-1α-/- ). We show that myeloid HIF-1α is not required for the containment of the infection, as both wild-type (WT) and mHIF-1α-/- mice mounted normal Th1 responses and maintained control of bacterial growth throughout infection. However, during chronic infection mHIF-1α-/- mice developed extensive lymphocytic inflammatory involvement of the interstitial lung tissue and died earlier than WT mice. These data support the hypothesis that HIF-1α activity coordinates the response of myeloid cells during M. tuberculosis infection to prevent excessive leucocyte recruitment and immunopathological consequences to the host.© 2019 John Wiley & Sons Ltd.
Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904637http://www.ncbi.nlm.nih.gov/pubmed/31606895
http://dx.doi.org/10.1111/imm.13131
