Duox and Jak/Stat signalling influence disease tolerance in Drosophila during Pseudomonas entomophila infection.

Disease tolerance describes an infected host's ability to maintain health independently of the ability to clear microbe loads. The Jak/Stat pathway plays a pivotal role in humoral innate immunity by detecting tissue damage and triggering cellular renewal, making it a candidate tolerance mechanism. Here, we find that in Drosophila melanogaster infected with Pseudomonas entomophila disrupting ROS -producing dual oxidase (duox) or the negative regulator of Jak/Stat Socs36E, render male flies less tolerant. Another negative regulator of Jak/Stat , G9a - which has previously been associated with variable tolerance of viral infections – did not affect the rate of mortality with increasing microbe loads compared to flies with functional G9a , suggesting it does not affect tolerance of bacterial infection as in viral infection. Our findings highlight that ROS production and Jak/Stat signalling influence the ability of flies to tolerate bacterial infection sex-specifically and may therefore contribute to sexually dimorphic infection outcomes in Drosophila. • The Jak/Stat pathway impacts disease tolerance during systemic infection with Pseudomonas entomophila. • Disrupting Duox or Socs36E render males less tolerant to systemic bacterial infection. • G9a does not affect tolerance during bacterial infection as it does during viral infection. [ABSTRACT FROM AUTHOR]