PROTEOME ANALYSIS OF HUMAN BRONCHIAL EPITHELIAL CELLS INFECTED WITH BORDETELLA PERTUSSIS

MARTINA DEBANDI; MANUELA GESELL SALAZAR; CARLOS BAROLI; CHRISTIAN HENTSCHKER; MARIELA CARRICA; FRANK SCHMIDT; MARÍA EUGENIA RODRÍGUEZ; UWE VÖLKER; SURMANN KRISTIN; YANINA LAMBERTI

Mar del Plata

Congreso; LXVI Reunion Anual de la Sociedad Argentina de Inmunologia; 2018

Sociedad Argentina de Inmunologia

Bordetella pertussis (Bp), the causative agent of whooping cough, survives within host cells potentially contributing to its ability to persist within hosts and populations. Pertussis toxin (PT) plays a major role in the modulation of macrophage responses and intracellular survival. The airway epithelium is also considered central to the orchestration of the immune responses, yet their responses to Bp have not been fully investigated. In this study, we examined the molecular responses of the human bronchial epithelial cell line 16HBE14o- to Bp infection by shotgun proteomics. To this end, 16HBE14o- cells were infected with Bp wild type (wt) or an isogenic mutant lacking PT (ΔPT) during 4.5 h and 8 h at a multiplicity of infection of one and the host response was compared to a similarly treated uninfected control. Among 2425 identified proteins, the abundance levels of 745 proteins were significantly altered by Bp infection compared with the control. GO biological term and pathways enrichment analysis of the proteins displaying altered levels by the DAtabase for Visualization and Integrative Discovery (DAVID) revealed a significant enrichment of proteins involved in cell adhesion mediated by integrin, phagosome, AMPK signaling pathway, receptor internalization, and regulation of immune response, among others. A role of PT in the up-regulation of integrin mediated cell adhesion and in the regulation of immune response was observed. PT was found involved in the upregulation of VLA-5, an integrin implicated in Bp invasion, suggesting that Bp promote its own internalization. Moreover, proteins related with the biological process antigen processing and presentation showed a decreased abundance after ΔPT infection compared to wt infection, suggesting that PT influences the efficiency of a T cell-mediated immune response. Overall, this study describes for the first time human protein alterations induced by Bp infection, thus providing new clues for understanding pertussis pathogenesis