An upside to chronic inflammation? Starvation reconfigures immune pathways in Manduca sexta, producing chronic inflammation that may help defend against bacterial infection
- 1Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
Abstract
Most animals face periods of food scarcity, and pathogens are ever-present. Therefore, selection will favour animals that can maintain immune defense during starvation, despite declining resources. Using the caterpillar Manduca sexta as a model system, we show how two days of starvation reconfigures the immune system. Metabolomic and proteomic analysis of the plasma showed that starvation shifted the immune system towards a more ‘pro-inflammatory’ state, with increased activity in the phenoloxidase/eumelanin pathways relative to controls. Melanization occurred more rapidly in starved caterpillars, demonstrating that these molecular changes had functional significance. This chronic inflammation correlated with a decline in the abundance of the important antioxidant glutathione (GSH) in the plasma. Increasing GSH in the plasma either by injection or diet reduced melanization in starved caterpillars, suggesting that the decline in GSH abundance could contribute to the increase in inflammation. Although starvation enhanced phenoloxidase pathway activity, it also reduced nodulation, suggesting a decline in cell-mediated immunity. Nevertheless, we found that starved caterpillars had fewer bacteria in their hemolymph (i.e., colony forming units, CFUs) 3 h after infection with live Bacillus cereus than did fed controls or weight-matched controls. However, increasing GSH in starved caterpillars increased mortality from B. cereus infection. We suggest that the upregulation of the phenoloxidase/eumelanin pathways during starvation is beneficial because it partially compensates for concurrent declines in other immune components. Without this chronic inflammation, our results suggest that caterpillars would experience an even greater decline in disease resistance during starvation.
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BibTeX
@article{adamo2026upside,
title = {{An upside to chronic inflammation? Starvation reconfigures immune pathways in Manduca sexta, producing chronic inflammation that may help defend against bacterial infection}},
author = {Shelley A. Adamo and Madeleine R. Burns and Megan H. Englehardt and Arisha Grabtchak and Rose Kearney and Claire A. E. Martin and Maya R. Richmond},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0358460},
url = {https://doi.org/10.1371/journal.pone.0358460},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An upside to chronic inflammation? Starvation reconfigures immune pathways in Manduca sexta, producing chronic inflammation that may help defend against bacterial infection
AU - Shelley A. Adamo
AU - Madeleine R. Burns
AU - Megan H. Englehardt
AU - Arisha Grabtchak
AU - Rose Kearney
AU - Claire A. E. Martin
AU - Maya R. Richmond
PY - 2026
DA - 2026/09/21
JO - PLOS One
DO - 10.1371/journal.pone.0358460
UR - https://doi.org/10.1371/journal.pone.0358460
AB - Most animals face periods of food scarcity, and pathogens are ever-present. Therefore, selection will favour animals that can maintain immune defense during starvation, despite declining resources. Using the caterpillar Manduca sexta as a model system, we show how two days of starvation reconfigures the immune system. Metabolomic and proteomic analysis of the plasma showed that starvation shifted the immune system towards a more ‘pro-inflammatory’ state, with increased activity in the phenoloxidase/eumelanin pathways relative to controls. Melanization occurred more rapidly in starved caterpillars, demonstrating that these molecular changes had functional significance. This chronic inflammation correlated with a decline in the abundance of the important antioxidant glutathione (GSH) in the plasma. Increasing GSH in the plasma either by injection or diet reduced melanization in starved caterpillars, suggesting that the decline in GSH abundance could contribute to the increase in inflammation. Although starvation enhanced phenoloxidase pathway activity, it also reduced nodulation, suggesting a decline in cell-mediated immunity. Nevertheless, we found that starved caterpillars had fewer bacteria in their hemolymph (i.e., colony forming units, CFUs) 3 h after infection with live Bacillus cereus than did fed controls or weight-matched controls. However, increasing GSH in starved caterpillars increased mortality from B. cereus infection. We suggest that the upregulation of the phenoloxidase/eumelanin pathways during starvation is beneficial because it partially compensates for concurrent declines in other immune components. Without this chronic inflammation, our results suggest that caterpillars would experience an even greater decline in disease resistance during starvation.
SN - 1932-6203
ER -