Characterization of bovine endometrial epithelial cell inflammatory response to Leptospira borgpetersenii serovar Hardjo

Authors: MOLINARI, PAULA - University Of Florida; Nally, Jarlath; BROMFIELD, JOHN - University Of Florida

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/31/2021
Publication Date: 8/4/2021
Citation: Molinari, P.C., Nally, J.E., Bromfield, J.L. 2021. Characterization of bovine endometrial epithelial cell inflammatory response to Leptospira borgpetersenii serovar Hardjo. Veterinary Immunology and Immunopathology. vol.2 issue 3 pgs 187-196. https://doi.org/10.1530/RAF-21-0012.
DOI: https://doi.org/10.1530/RAF-21-0012

Interpretive Summary: Leptospirosis is a zoonotic disease caused by an atypical bacterium, Leptospira. Leptospirosis causes abortion, premature birth, and stillbirth in cattle, but the mechanisms remain unclear. Infected cattle shed Leptospira intermittently and present a range of clinical symptoms, making diagnosis difficult. The primary route of Leptospira transmission in any animal is colonization of the renal tubule and excretion by urine, however Leptospira can also colonize the female reproductive tract of cows and can be transmitted by semen. Vaccination against Leptospira in the United States is routine in cattle, but immunity is not guaranteed. In order to investigate the association between Leptospira and bovine reproduction failure, a cell culture model was used to assess the ability of Leptospira to initiate an innate inflammatory response from bovine uterine endometrial cells. Cells were exposed to either heat-killed Leptospira, Leptospira outer membrane, Escherichia coli LPS, Pam3CSK4 or medium alone for 24 hours. Exposure of bovine endometrial epithelial cells or human monocytes to E. coli LPS or Pam3CSK4 increased expression of inflammatory signals compared to control cells. Exposure of bovine endometrial epithelial cells or human monocytes to heat-killed Leptospira or Leptospira outer membrane did not alter the expression of inflammatory mediators. Understanding the interaction between Leptospira and the female reproductive tract is important in determining the mechanisms of Leptospirosis associated reproductive failure.

Technical Abstract: Leptospirosis causes abortion, premature birth, and stillbirth in cattle, but the mechanisms remain unclear. Infected cattle shed Leptospira intermittently and present a range of clinical symptoms, making diagnosis difficult. The primary route of Leptospira transmission in any animal is colonization of the renal tubule and excretion by urine, however Leptospira can also colonize the female reproductive tract of cows and can be transmitted by semen. Vaccination against Leptospira in the United States is routine in cattle, but immunity is not guaranteed. The cell wall of Leptospira contains Toll-like receptors agonists including peptidoglycan and lipopolysaccharide. The capacity of Leptospira to initiate an innate inflammatory response from uterine endometrial cells is unknown but may be a cause of reproductive failure. Using cell culture, we tested the capacity of bovine endometrial epithelial cells or human monocytes to elicit an inflammatory response to Leptospira borgpetersenii serovar Hardjo strain TC273. Cells were exposed to either heat-killed Leptospira, Leptospira outer membrane, Escherichia coli LPS, Pam3CSK4 or medium alone for 24 hours. Exposure of bovine endometrial epithelial cells or human monocytes to E. coli LPS or Pam3CSK4 increased expression of IL1B, IL6 and CXCL8 compared to control cells. Exposure of bovine endometrial epithelial cells or human monocytes to heat-killed Leptospira or Leptospira outer membrane did not alter the expression of inflammatory mediators. Understanding the interaction between Leptospira and the female reproductive tract is important in determining the mechanisms of Leptospirosis associated reproductive failure.