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Tolerance to Haemophilus influenzae infection in human epithelial cells: Insights from a primary cell-based model.
Kappler, Ulrike; Henningham, Anna; Nasreen, Marufa; Yamamoto, Ayaho; Buultjens, Andrew H; Stinear, Timothy P; Sly, Peter; Fantino, Emmanuelle.
Afiliación
  • Kappler U; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia.
  • Henningham A; Child Health Research Centre, The University of Queensland, South Brisbane, Australia.
  • Nasreen M; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia.
  • Yamamoto A; Child Health Research Centre, The University of Queensland, South Brisbane, Australia.
  • Buultjens AH; Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
  • Stinear TP; Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
  • Sly P; Child Health Research Centre, The University of Queensland, South Brisbane, Australia.
  • Fantino E; Child Health Research Centre, The University of Queensland, South Brisbane, Australia.
PLoS Pathog ; 20(7): e1012282, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38990812
ABSTRACT
Haemophilus influenzae is a human respiratory pathogen and inhabits the human respiratory tract as its only niche. Despite this, the molecular mechanisms that allow H. influenzae to establish persistent infections of human epithelia are not well understood. Here, we have investigated how H. influenzae adapts to the host environment and triggers the host immune response using a human primary cell-based infection model that closely resembles human nasal epithelia (NHNE). Physiological assays combined with dualRNAseq revealed that NHNE from five healthy donors all responded to H. influenzae infection with an initial, 'unproductive' inflammatory response that included a strong hypoxia signature but did not produce pro-inflammatory cytokines. Subsequently, an apparent tolerance to large extracellular and intraepithelial burdens of H. influenzae developed, with NHNE transcriptional profiles resembling the pre-infection state. This occurred in parallel with the development of intraepithelial bacterial populations, and appears to involve interruption of NFκB signalling. This is the first time that large-scale, persistence-promoting immunomodulatory effects of H. influenzae during infection have been observed, and we were able to demonstrate that only infections with live, but not heat-killed H. influenzae led to immunomodulation and reduced expression of NFκB-controlled cytokines such as IL-1ß, IL-36γ and TNFα. Interestingly, NHNE were able to re-activate pro-inflammatory responses towards the end of the 14-day infection, resulting in release of IL-8 and TNFα. In addition to providing first molecular insights into mechanisms enabling persistence of H. influenzae in the host, our data further indicate the presence of infection stage-specific gene expression modules, highlighting fundamental similarities between immune responses in NHNE and canonical immune cells, which merit further investigation.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Haemophilus influenzae / Células Epiteliales / Infecciones por Haemophilus Límite: Humans Idioma: En Revista: PLoS Pathog Año: 2024 Tipo del documento: Article País de afiliación: Australia

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Haemophilus influenzae / Células Epiteliales / Infecciones por Haemophilus Límite: Humans Idioma: En Revista: PLoS Pathog Año: 2024 Tipo del documento: Article País de afiliación: Australia