The Inflammatory Response to Birth Requires MyD88 and is Driven by Both Mother and Offspring.

Details

• Alternative Title:
  Brain, Behavior, and Immunity, 2024, v. 115: The Inflammatory Response to Birth Requires MyD88 and is Driven by Both Mother and Offspring.
• Journal Article:
  Brain, Behavior, and Immunity
• Personal Author:
  Gray, Jennifer M. ; Major, Kharli ; Castillo-Ruiz, Alexandra ; Shipley, Michael ; Gangappa, Shivaprakash ; Forger, Nancy G.
• Description:
  Birth is an inflammatory event for the newborn, characterized by elevations in interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α peripherally and/or centrally, as well as changes in brain microglia. However, the mechanism(s) underlying these responses is unknown. Toll-like receptors (TLRs) play crucial roles in innate immunity and initiate inflammatory cascades upon recognition of endogenous or exogenous antigens. Most TLR signaling depends on the adaptor molecule myeloid differentiation primary response 88 (MyD88). We independently varied MyD88 gene status in mouse dams and their offspring to determine whether the inflammatory response to birth depends on MyD88 signaling and, if so, whether that signaling occurs in the offspring, the mother, or both. We find that the perinatal surges in plasma IL-6 and brain expression of TNF-α depend solely on MyD88 gene status of the offspring, whereas postnatal increases in plasma IL-10 and TNF-α depend on MyD88 in both the pup and dam. Interestingly, MyD88 genotype of the dam primarily drives differences in offspring brain microglial density and has robust effects on developmental neuronal cell death. Milk cytokines were evaluated as a possible source of postnatal maternal influence; although we found high levels of CXCL1/GROα and several other cytokines in ingested post-partum milk, their presence did not require MyD88. Thus, the inflammatory response previously described in the late-term fetus and newborn depends on MyD88 (and, by extension, TLRs), with signaling in both the dam and offspring contributing. Unexpectedly, naturally-occuring neuronal cell death in the newborn is modulated primarily by maternal MyD88 gene status.
• Content Notes:
  Author manuscript
• Subjects:
  • Animals
  • Female
  • Mice
  • Pregnancy
  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • Interleukin-10
  • Interleukin-6
  • Mice, Inbred C57BL
  • Mothers
  More +
• Keywords:
  • Toll-like receptors
  • MyD88
  • Birth
  • Parturition
  • Neuroinflammation
  • Cytokines
  • Microglia
  • Cell death
  • Milk
• Source:
  Brain, Behavior, and Immunity, 2024, v. 115
• DOI:
  https://doi.org/10.1016/j.bbi.2023.11.011
• ISSN:
  0889-1591 ; 1090-2139
• Pubmed ID:
  37967662
• Pubmed Central ID:
  PMC11913035
• Document Type:
  Text
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  617-630 (30 pdf pages)
• Volume:
  115
• Download URL:
  https://stacks.cdc.gov/view/cdc/262140/cdc_262140_DS1.pdf
• File Type:
  [PDF - 3.06 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:6292a2c0e87fa9bbed23af06e5769909c0ea7f98151da8fbfc6f7e007fc9f4149b33a25ebb692fb60d8a02a28abbffc50a52c3c084dd982b2d7095e92f12b593