Sex Differences in the Th2 Lung-Brain Axis Response to Aspergillus Versicolor Inhalation in C57BL/6J Mice

Details

• Personal Author:
  Ahmed, C. ; Beezhold, Donald H. ; Blackwood, C. ; Block, M. L. ; Chittum, G. ; Croston, Tara L. ; Dunbar, G. ; Gomez Ponce, T. ; Green, Brett J. ; Johnson, J. A. ; Lemons, Angela R. ; Malley, J. ; Miller, M. M. ; Tsoggerel, A. ; Weaver, K. L. ; Woodward, W.
• Description:
  Alzheimer's disease (AD) is a devastating form of dementia that includes a dysregulated microglial phenotype and maladaptive immune cell trafficking. Yet the identity of environmental exposures that are culpable in this disruption, and in peripheral immune responses regulating the brain remain poorly understood. Aspergillus versicolor is a common filamentous fungi found in damp indoor environments, where human inhalation exposure has been linked to asthma, a respiratory disease. Asthma is also associated with an increased AD risk. Previously, we have demonstrated that A. versicolor exposure results in transcriptional neuroimmune and neurochemical changes in the brain. According to the lung-brain-axis hypothesis, the pulmonary response to environmental exposures dysregulates microglia through changes in peripheral immune cells and circulating factors that regulate CNS health and disease. However, the role of sex differences in this process is largely unknown. Consistent with reports from female B6C3F1/N mice, male 5xFAD mice exposed to nose-only filtered air or A. versicolor (3 × 105 spores) two times a week for 13 weeks, resulted in A. versicolor-induced humoral changes indicative of a Th2 pulmonary response. Unfortunately, the estrogen response element in the promotor of the 5xFAD mouse confounds and precludes any analysis of females in this strain. As such, the C57BL/6J control strain was used to explore sex differences in the humoral and microglial responses to A. versicolor. Here we found sex differences in the changes in cortical microglial morphology, where male mice showed a significant increase in microglia volume after 13 weeks of A. versicolor exposure when compared to filtered air; but female mice failed to show a significant response. Furthermore, data revealed a significant increase in circulating factors IL-5, IP-10, IL-17, and TNFa in male mice exposed to A. versicolor, whereas these effects were absent in the female mice. Interestingly, during reproductive years, females often have a more robust immune response than males. However, when reproductive females do experience adverse reactions, the severity is often greater than affected males. Taken together, these findings support that the humoral and microglial response to A. versicolor is dysregulated in female C57BL/6J, highlighting the presence of sex differences in the Th2 Lung-Brain axis. Given the increased female risk in AD, further studies are needed to explore how these differences translate to amyloid and tau pathology. [Description provided by NIOSH]
• Subjects:
  Animals Environmental Exposure Fungi Immune System Nervous System Occupational Health Respiratory System Safety Sex Characteristics Toxicology
• Keywords:
  Alzheimer's Disease Animal Studies Author Keywords: Environmental Exposure Environmental Exposure Immune Reaction Inhalation Studies Neurotoxicology Respiratory Toxicology Sex Factors
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Indiana ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  3 pdf pages
• Volume:
  192
• NIOSHTIC Number:
  nn:20067236
• Citation:
  Toxicologist 2023 Mar; 192(S2):45-46
• Federal Fiscal Year:
  2023
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:081fe5ca0140d0e7700b9fe42510c747020fe983a85249a95840f68956fead316a83eabbcc8121f045d231a1ac54b913aa19dfd0edf9ab185cc141df79ea62eb
• Download URL:
  https://stacks.cdc.gov/view/cdc/230666/cdc_230666_DS1.pdf
• File Type:
  [PDF - 1.39 MB ]