Myeloid HIF-1α regulates pulmonary inflammation during experimental Mycobacterium tuberculosis infection

The transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key regulator of the response and function of myeloid cells in hypoxic and inflammatory microenvironments. To define the role of HIF-1 alpha in tuberculosis, the progression of aerosol Mycobacterium tuberculosis infection was analysed in mice deficient in HIF-1 alpha in the myeloid lineage (mHIF-1 alpha(-/-)). We show that myeloid HIF-1 alpha is not required for the containment of the infection, as both wild-type (WT) and mHIF-1 alpha(-/-) mice mounted normal Th1 responses and maintained control of bacterial growth throughout infection. However, during chronic infection mHIF-1 alpha(-/-) mice developed extensive lymphocytic inflammatory involvement of the interstitial lung tissue and died earlier than WT mice. These data support the hypothesis that HIF-1 alpha activity coordinates the response of myeloid cells during M. tuberculosis infection to prevent excessive leucocyte recruitment and immunopathological consequences to the host.