A finely-tuned innate immune response plays a pivotal role in protecting host against bacterial invasion during
periodontal disease progression.
Hyperlipidemia has been suggested to exacerbate periodontal health condition. However, the underlying mechanism has not been addressed. In the present study, we investigated the effect of
hyperlipidemia on innate immune responses to periodontal pathogen Porphyromonas gingivalis
infection.
Apolipoprotein E-deficient and wild-type mice at the age of 20 weeks were used for the study. Peritoneal macrophages were isolated and subsequently used for the study of viable P. gingivalis
infection.
ApoE(-/-) mice demonstrated inhibited iNOS production and impaired clearance of P. gingivalis in vitro and in vivo; furthermore,
ApoE(-/-) mice displayed disrupted
cytokine production pattern in response to P. gingivalis, with a decreased production of
tumor necrosis factor-α,
interleukin-6 (IL-6), IL-1β and
monocyte chemotactic protein-1. Microarray data demonstrated that
Toll-like receptor (TLR) and
NOD-like receptor (NLR) pathway were altered in
ApoE(-/-) mice macrophages; further analysis of
pattern recognition receptors (
PRRs) demonstrated that expression of triggering receptors on myeloid cells-1 (TREM-1), an amplifier of the TLR and NLR pathway, was decreased in
ApoE(-/-) mice macrophages, leading to decreased recruitment of NF-κB onto the promoters of the TNF-α and
IL-6. Our data suggest that in
ApoE(-/-) mice
hyperlipidemia disrupts the expression of
PRRs, and cripples the host's capability to generate sufficient innate immune response to P. gingivalis, which may facilitate immune evasion, subgingival colonization and establishment of P. gingivalis in the periodontal niche.