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JNK signaling regulates reproductive trade-offs after Plasmodium infection in the malaria mosquito

Lombardi, M.; Accoti, A.; Scarpelli, P.; Iacomelli, G.; Pazzagli, L.; Turco, A.; Monacchia, G.; Ferracchiato, S.; Rinvee, T. A.; Peng, D.; Vidoudez, C.; Shaw, W. R.; Catteruccia, F.; Spaccapelo, R.; Peirce, M. J.

2025-09-07 zoology
10.1101/2025.09.03.673998 bioRxiv
Show abstract

Environmental stress can limit mammalian reproduction by affecting production of sexual steroid hormones. Here we reveal a similar mechanism in the malarial mosquito Anopheles gambiae: activation of the stress-sensitive c-Jun N-terminal kinase, JNK, constrains reproductive investment by suppressing production of ecdysteroids that orchestrate egg development in this species. We show that infection with Plasmodium berghei parasites increases JNK signalling in the reproductive tract causing a JNK-dependent reduction in both egg development and mosquito survival. Moreover, JNK signaling supresses expression of Cyp315a1 (AGAP000284), a rate-limiting enzyme in ecdysteroid synthesis, a transcriptional change reflected in reduced ecdysteroid production following an infected blood meal. A similar mechanism limits egg production under other stressors (heat stress, or ectopic activation of JNK signaling). Together, these data reveal a regulatory circuit whereby Plasmodium infection curtails reproductive investment in an important vector of human malaria, one that may be applicable to environmental stressors more generally.

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