A novel role of TLR9 in peritoneal B cell in regulating host defense during polymicrobial sepsis
Author(s):
Li Xu, University of Pittsburgh School of Medicine;Union Hospital,Tongji Medical College,Hua zhong University of Science and Technology; Meihong Deng, University of Pittsburgh school of Medine; Rosemary Hoffman, University of Pittsburgh School of Medicine; Patricia Loughran, University of Pittsburgh School of Medicine; Timothy Billiar, University of Pittsburgh
Background:
TLR9 is known to play important roles in sepsis.TLR9 deficient (TLR9-/-)mice are resistant to polymicrobial sepsis.
Hypothesis:
However, the mechanisms and biological pathways by which TLR9 regulates host defense are yet to be identified.
Methods:
To investigate this, mice were subjected to a clinical relevant polymicrobial sepsis model, cecal ligation and puncture(CLP), for 18 hours.
Results:
As expected, global deletion of TLR9 increased survival and decreased bacterial load in peritoneal as well as systemic inflammation after CLP. The number of peritoneal PMNs in TLR9-/- mice was significantly higher than in WT mice after CLP (WT CLP 9.26±1.03*106 ;TLR9 KO CLP 16.2±5.08*106), suggesting that TLR9 may regulate host defense via PMN recruitment. However, specifically knockout of TLR9 in myeloid cells was not phenocopy of global TLR9-/- after CLP; suggesting that TLR9 on myeloid cell did not play critical roles in host defense. Interestingly, the number of peritoneal B cells assessed by flow cytometry was significantly higher in TLR9-/- mice than their control at baseline as well as after CLP (Number of peritoneal B cells: WT Control 4.85±1.46*105; TLR9 KO Control 33.8±5.44*105;WT CLP 1.39±1.12*105;TLR9 KO CLP 6.42±3.07*105).Importantly, the circulating level of natural antibody IgM, which is important for opsonization of bacteria for PMN phagocytosis, was significantly increased in TLR9-/- mice than their control at baseline and after CLP.
Conclusions:
Our data suggest an unrecognized role of TLR9 in B cells in regulation of host defense via modulation of IgM secretion from B cell.