Productive and Penicillin-Stressed Chlamydia pecorum Infection Induces Nuclear Factor Kappa B Activation and Interleukin-6 Secretion In Vitro.

Cory A Leonard,Robert V Schoborg,Nicole Borel

doi:10.3389/fcimb.2017.00180

Abstract

Nuclear factor kappa B (NFκB) is an inflammatory transcription factor that plays an important role in the host immune response to infection. The potential for chlamydiae to activate NFκB has been an area of interest, however most work has focused on chlamydiae impacting human health. Given that inflammation characteristic of chlamydial infection may be associated with severe disease outcomes or contribute to poor overall fitness in farmed animals, we evaluated the ability of porcine chlamydiae to induce NFκB activation in vitro. C. pecorum infection induced both NFκB nuclear translocation and activation at 2 hours post infection (hpi), an effect strongly enhanced by suppression of host de novo protein synthesis. C. suis and C. trachomatis showed less capacity for NFκB activation compared to C. pecorum, suggesting a species-specific variation in NFκB activation. At 24 hpi, C. pecorum induced significant NFκB activation, an effect not abolished by penicillin (beta lactam)-induced chlamydial stress. C. pecorum-dependent secretion of interleukin 6 was also detected in the culture supernatant of infected cells at 24 hpi, and this effect, too, was unchanged by penicillin-induced chlamydial stress. Taken together, these results suggest that NFκB participates in the early inflammatory response to C. pecorum and that stressed chlamydiae can promote inflammation.

Highlights

The chlamydiae, obligate intracellular Gram-negative bacterial pathogens, cause a broad range of diseases in non-human animals and humans
Immunofluorescence (IF) microscopy was used to evaluate the ability of porcine chlamydiae species C. suis S45/6 strain (Kaltenboeck et al, 1993) and C. pecorum 1710S strain and the human pathogen C. trachomatis serovar E (Holt et al, 1967) to induce nuclear translocation of the inflammatory transcription factor NFκB p65 subunit
Chlamydial infections in animals are common, and inflammatory in nature, little evaluation of the role of NFκB in the pathogenesis of agriculturally important chlamydial species has been undertaken to date

Summary

Introduction

The chlamydiae, obligate intracellular Gram-negative bacterial pathogens, cause a broad range of diseases in non-human animals and humans. Various stressors, including host immune response factors, nutrient deprivation, beta lactam antibiotic exposure, or co-infection with viruses or parasites, are capable of interrupting RB replicative division and maturation to EBs and inducing aberrant body (AB) formation. Chlamydia pecorum Induces NFκB Activation of the stressor, normal chlamydial development resumes, and eventual release of infectious EBs continues. This divergence from the normal developmental cycle results in a reversible lack of infectivity, termed chlamydial persistence or the chlamydial stress response (Hogan et al, 2004; Wyrick, 2010; Schoborg, 2011; Bavoil, 2014). While some chlamydial forms consistent with AB have been reported in both human (Borel et al, 2008) and animal (Pospischil et al, 2009) tissue samples, and chlamydial persistence has been induced experimentally in mice, wherein it limited the efficacy of subsequent azithromycin treatment (Phillips Campbell et al, 2012; Phillips-Campbell et al, 2014), the biological significance of the chlamydial stress response in natural infections is unknown

Objectives

Methods

Results

Conclusion