This is a second paper about neutrophils in Nature this week (advanced online publication). Quite interesting and surprising. It showed that autophagy molecule Atg5 has unique [autophagy-independent] role in protecting against neutrophil-driven immunopathology during M. tuberculosis lung infection.
Initially, the authors showed that myeloid cell-specific deletion of Atg5 (LysM-Cre Atg5fl/fl) made mice highly susceptible to M. tuberculosis infection (that was expected based on earlier studies).
Unexpectedly and surprisingly, however, mice singly deficient for other autophagy components showed normal response to M. tuberculosis infection, implying unique, autophagy-independent role for Atg5 during M. tuberculosis infection.
Indeed, LysM-Cre Atg5fl/fl mice showed more severe M. tuberculosis-associated immunopathology and neutrophil infiltration (even though LysM-Cre Atg5fl/fl mice did not harbor substantially more M. tuberculosis).
Furthermore, LysM-Cre Atg5fl/fl mice depleted of neutrophils were protected from lung pathology during M. tuberculosis infection.
Finally, neutrophil-specific deletion of Atg5 (MRP8-Cre Atg5fl/fl mice) confirmed pathological role of Atg5-deficient neutrophils during M. tuberculosis infection.
In summary, this study provides evidence for autophagy-independent role of Atg5 deficiency in neutrophils during M. tuberculosis infection. It appears that neutrophils recruited to the sites of M. tuberculosis infection contribute to tissue pathology rather than provide protection in absence of Atg5. Earlier it was assumed that Atg5 played a protective role during infection purely via its involvement in autophagy formation. However, this new study point to a more complex role of Atg5.
David Usharauli
Unexpectedly and surprisingly, however, mice singly deficient for other autophagy components showed normal response to M. tuberculosis infection, implying unique, autophagy-independent role for Atg5 during M. tuberculosis infection.
Finally, neutrophil-specific deletion of Atg5 (MRP8-Cre Atg5fl/fl mice) confirmed pathological role of Atg5-deficient neutrophils during M. tuberculosis infection.
In summary, this study provides evidence for autophagy-independent role of Atg5 deficiency in neutrophils during M. tuberculosis infection. It appears that neutrophils recruited to the sites of M. tuberculosis infection contribute to tissue pathology rather than provide protection in absence of Atg5. Earlier it was assumed that Atg5 played a protective role during infection purely via its involvement in autophagy formation. However, this new study point to a more complex role of Atg5.
David Usharauli
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