The role of microglia in 67NR mammary tumor-induced suppression of brain responses to immune challenges in female mice.

Autor: Otto-Dobos LD; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA., Santos JC; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA., Strehle LD; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA., Grant CV; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA., Simon LA; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA., Oliver B; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA., Godbout JP; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA.; Department of Neuroscience, The Ohio State University, Columbus, Ohio, USA.; Chronic Brain Injury Program, The Ohio State University, Columbus, Ohio, USA., Sheridan JF; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA.; Department of Neuroscience, The Ohio State University, Columbus, Ohio, USA.; Division of Biosciences College of Dentistry, The Ohio State University, Columbus, Ohio, USA., Barrientos RM; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA.; Department of Neuroscience, The Ohio State University, Columbus, Ohio, USA.; Chronic Brain Injury Program, The Ohio State University, Columbus, Ohio, USA.; Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, Ohio, USA., Glasper ER; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA.; Department of Neuroscience, The Ohio State University, Columbus, Ohio, USA., Pyter LM; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA.; Department of Neuroscience, The Ohio State University, Columbus, Ohio, USA.; Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, Ohio, USA.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Oct; Vol. 168 (10), pp. 3482-3499. Date of Electronic Publication: 2023 May 10.
DOI: 10.1111/jnc.15830
Abstrakt: It is poorly understood how solid peripheral tumors affect brain neuroimmune responses despite the various brain-mediated side effects and higher rates of infection reported in cancer patients. We hypothesized that chronic low-grade peripheral tumor-induced inflammation conditions microglia to drive suppression of neuroinflammatory responses to a subsequent peripheral immune challenge. Here, Balb/c murine mammary tumors attenuated the microglial inflammatory gene expression responses to lipopolysaccharide (LPS) and live Escherichia coli (E. coli) challenges and the fatigue response to an E. coli infection. In contrast, the inflammatory gene expression in response to LPS or a toll-like receptor 2 agonist of Percoll-enriched primary microglia cultures was comparable between tumor-bearing and -free mice, as were the neuroinflammatory and sickness behavioral responses to an intracerebroventricular interleukin (IL)-1β injection. These data led to the hypothesis that Balb/c mammary tumors blunt the neuroinflammatory responses to an immune challenge via a mechanism involving tumor suppression of the peripheral humoral response. Balb/c mammary tumors modestly attenuated select circulating cytokine responses to LPS and E. coli challenges. Further, a second mammary tumor/mouse strain model (E0771 tumors in C57Bl/6 mice) displayed mildly elevated inflammatory responses to an immune challenge. Taken together, these data indicate that tumor-induced suppression of neuroinflammation and sickness behaviors may be driven by a blunted microglial phenotype, partly because of an attenuated peripheral signal to the brain, which may contribute to infection responses and behavioral side effects reported in cancer patients. Finally, these neuroimmune effects likely vary based on tumor type and/or host immune phenotype.
(© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)
Databáze: MEDLINE
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