ABSTRACT
An animal's immune function is vital for survival but is potentially metabolically expensive. Some pathogens can manipulate their hosts' immune and metabolic responses. One example is Mycoplasma gallisepticum (MG), which infects both the respiratory system and conjunctiva of the eye in house finches (Haemorhous mexicanus). MG has been shown to exhibit immune- and metabolic-suppressive properties, but the physiological mechanisms are still unknown. Recent studies demonstrated that mitochondria could serve as powerhouses for both ATP production and immunity, notably inflammatory processes, by regulating complex II and its metabolites. Consequently, in this study, we investigate the short-term (3 days post-inoculation) and long-term (34 days post-inoculation) effects of MG infection on the hepatic mitochondrial respiration of house finches from two populations infected with two different MG isolates. After short-term infection, MG-infected birds had significantly lower state 2 and state 4 respiration, but only when using complex II substrates. After long-term infection, MG-infected birds exhibited lower state 3 respiration with both complex I and II substrates, resulting in a lower respiratory control ratio compared with uninfected controls, which aligned with the hypothesized metabolic-suppressive properties of MG. Interestingly, there were limited differences in mitochondrial respiration regardless of house finch population of origin, MG isolate and whether birds recovered from infection or not. We propose that MG targets mitochondrial complex II for its immune-suppressive properties during the early stages of infection and inhibits mitochondrial respiration for its metabolic-suppressive properties at a later stage of infection, both of which should delay recovery of the host and extend infectious periods.
Footnotes
Author contributions
Conceptualization: A.E.H., J.S.A., Y.Z.; Data curation: C.R., E.T., A.E.H., J.S.A., Y.Z.; Formal analysis: Y.Z., J.S.A.; Funding acquisition: J.S.A., Y.Z.; Investigation: C.R., E.T., J.S.A., Y.Z.; Methodology: J.S.A., Y.Z.; Project administration: Y.Z.; Resources: Y.Z., J.S.A.; Supervision: J.S.A., Y.Z.; Validation: J.S.A., Y.Z.; Visualization: Y.Z.; Writing – original draft: C.R., Y.Z.; Writing – review & editing: C.R., E.T., A.E.H., J.S.A., Y.Z.
Funding
This research was funded by National Science Foundation grants IOS2224556 and IOS2037735 to Y.Z. and IOS1950307 to J.S.A.
Data and resource availability
All relevant data can be found within the article and its supplementary information.