Abstract
Using the subcutaneous chamber model of infection, we showed previously that a mixture of four endodontic pathogens (EP: P. intermedia, F. nucleatum, S. intermedius and P. micra) are able to persist without clearance for up to seven days, while a non-pathogenic oral species, S. mitis, was substantially cleared in this time. Here we have compared the cytokine response inside the chambers against these microorganisms. A majority of cytokines tested (17/24) showed different patterns of expression. Several cytokines had a peak of expression at 2 h after infection in response to the EP, while none showed this pattern in S. mitis infections. Chemokines were uniformly present at similar or higher levels in response to S. mitis, with redundant expression of CXCR2 ligands, while several growth/survival factors were present at higher levels in EP infections. Protease activity expressed by EP may be responsible for the lower levels of some chemokines. T-cell associated cytokines were in general expressed at extremely low levels, and did not differ between the two infections. The inflammatory markers IL-6, IL-1α and IL1-β were expressed at similar levels in both infections at early times, while TNFα was preferentially present in S. mitis infections. In EP infected chambers, reciprocal changes in levels of IL-6 and IL-1α were observed at later times suggesting a switch in the inflammatory response. Analysis of the cytokine response to infection with the individual species from the EP mix suggests that P. intermedia drives this inflammatory switch. Together these results show a surprising level of divergence of the host response to pathogenic and non-pathogenic organisms associated with oral infections, and supports a dominant effect of P. intermedia in polymicrobial endodontic infections.
Highlights
Endodontic infections are always polymicrobial [1], and can induce an intense host inflammatory response leading to pulpitis and necrosis [2]
We discovered that endodontic species associated with human endodontic infections, Prevotella intermedia, disrupt the host response by damaging or killing the infiltrating neutrophils, preventing them from carrying out anti-bacterial functions [11]
Chambers were infected with either a mixture of four endodontic pathogens: P. intermedia, F. nucleatum, S. intermedius, and P. micra (EP), which have been well documented to cause periapical lesions and associated bone loss in mice [7, 9, 14], or a non-pathogenic oral bacterial species Streptococcus mitis, a commensal oral organism not strongly associated with oral infections
Summary
Endodontic infections ( known as apical periodontitis) are always polymicrobial [1], and can induce an intense host inflammatory response leading to pulpitis and necrosis [2]. Endodontic diseases are common, with lifetime prevalence estimates as high as 20–100% infections per individual [3]. The innate immune response to microbial species involved in the etiology of PLOS ONE | DOI:10.1371/journal.pone.0132752. National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health
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