Lipopolysaccharides from Bordetella pertussis and Bordetella parapertussis Differently Modulate Human Dendritic Cell Functions Resulting in Divergent Prevalence of Th17-Polarized Responses

Abstract

Bordetella pertussis and B. parapertussis are the etiological agents of pertussis, yet the former has a higher incidence and is the cause of a more severe disease, in part due to pertussis toxin. To identify other factors contributing to the different pathogenicity of the two species, we analyzed the capacity of structurally different lipooligosaccharide (LOS) from B. pertussis and LPS from B. parapertussis to influence immune functions regulated by dendritic cells. Either B. pertussis LOS and B. parapertussis LPS triggered TLR4 signaling and induced phenotypic maturation and IL-10, IL-12p40, IL-23, IL-6, and IL-1β production in human monocyte-derived dendritic cells (MDDC). B. parapertussis LPS was a stronger inducer of all these activities as compared with B. pertussis LOS, with the notable exception of IL-1β, which was equally produced. Only B. parapertussis LPS was able to induce IL-27 expression. In addition, although MDDC activation induced by B. parapertussis LPS was greatly dependent on soluble CD14, B. pertussis LOS activity was CD14-independent. The analysis of the intracellular pathways showed that B. parapertussis LPS and B. pertussis LOS equally induced IκBα and p38 MAPK phosphorylation, but B. pertussis LOS triggered ERK1/2 phosphorylation more rapidly and at higher levels than B. parapertussis LPS. Furthermore, B. pertussis LOS was unable to induce MyD88-independent gene induction, which was instead activated by B. parapertussis LPS, witnessed by STAT1 phosphorylation and induction of the IFN-dependent genes, IFN regulatory factor-1 and IFN-inducible protein-10. These differences resulted in a divergent regulation of Th cell responses, B. pertussis LOS MDDC driving a predominant Th17 polarization. Overall, the data observed reflect the different structure of the two LPS and the higher Th17 response induced by B. pertussis LOS may contribute to the severity of pertussis in humans.

Pertussis Toxin Inhibits Early Chemokine Production To Delay Neutrophil Recruitment in Response toBordetella pertussisRespiratory Tract Infection in Mice

“…Nevertheless, one role for PT soon after B. pertussis infection may be to modulate inflammatory responses (including chemokine upregulation and neutrophil recruitment) mediated by LPS-TLR4 signaling. Although we used E. coli LPS in this study rather than B. pertussis LPS, both molecules are known to signal through TLR4, and a recent report demonstrated that E. coli LPS was a more potent stimulator of several proinflammatory responses than B. pertussis LPS (13), underscoring the inhibitory capacity of PT in this signaling pathway. We are currently attempting to dissect the TLR4 signaling pathway to determine how PT-sensitive heterotrimeric G i proteins may be involved in generating these responses.…”

IL-17A–Producing γδT Cells Promote CTL Responses against Listeria monocytogenes Infection by Enhancing Dendritic Cell Cross-Presentation

“…by gdT cells alone is sufficient for optimal CD8 + T cell priming. So, we propose that early production of IL-17A by innate gdT cells contributes to the adaptive immune response that clears the invading pathogens, whereas uncontrolled IL-17A production by Th17 cells at late stages of infection may risk exaggerated immune responses (55) and autoimmune diseases (56).…”

Attenuated Bordetella pertussis Vaccine Candidate BPZE1 Promotes Human Dendritic Cell CCL21-Induced Migration and Drives a Th1/Th17 Response

“…Studies are needed to unveil the role of other components, including filamentous hemagglutinin, adenylate cyclase toxin, and lipooligosaccharide, all described as inducers of DCs with a tolerogenic phenotype (10,12,13,39,40).…”

“…In particular, our studies shed light on the contribution of several virulence factors, such as adenylate cyclase toxin (9-11), lipooligosaccharide (12,13), and PT (14,15).…”