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Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response.
Rodel, Hylton E; Ferreira, Isabella A T M; Ziegler, Carly G K; Ganga, Yashica; Bernstein, Mallory; Hwa, Shi-Hsia; Nargan, Kievershen; Lustig, Gila; Kaplan, Gilla; Noursadeghi, Mahdad; Shalek, Alex K; Steyn, Adrie J C; Sigal, Alex.
Afiliación
  • Rodel HE; Africa Health Research Institute, Durban, South Africa.
  • Ferreira IATM; Division of Infection and Immunity, University College London, London, United Kingdom.
  • Ziegler CGK; Africa Health Research Institute, Durban, South Africa.
  • Ganga Y; Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA, United States.
  • Bernstein M; Department of Chemistry, Institute for Medical Engineering and Sciences, MIT, Cambridge, MA, United States.
  • Hwa SH; Broad Institute of MIT and Harvard, Cambridge, MA, United States.
  • Nargan K; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, United States.
  • Lustig G; Africa Health Research Institute, Durban, South Africa.
  • Kaplan G; Africa Health Research Institute, Durban, South Africa.
  • Noursadeghi M; Africa Health Research Institute, Durban, South Africa.
  • Shalek AK; Division of Infection and Immunity, University College London, London, United Kingdom.
  • Steyn AJC; Africa Health Research Institute, Durban, South Africa.
  • Sigal A; Africa Health Research Institute, Durban, South Africa.
Front Microbiol ; 12: 757134, 2021.
Article en En | MEDLINE | ID: mdl-34925266
Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggregated Mtb relative to phagocytosis of non-aggregated single or multiple bacilli. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNFα signaling via the NFκB pathway. These pathways were significantly more upregulated relative to infection with single or multiple non-aggregated bacilli per cell. Phagocytosis of aggregates led to a decreased phagosome acidification on a per bacillus basis and increased phagocyte cell death, which was not observed when Mtb aggregates were heat killed prior to phagocytosis. Mtb aggregates, observed in a granuloma from a patient, were found surrounding a lesion cavity. These observations suggest that TB aggregation may be a mechanism for pathogenesis. They raise the possibility that aggregated Mtb, if spread from individual to individual, could facilitate increased inflammation, Mtb growth, and macrophage cell death, potentially leading to active disease, cell necrosis, and additional cycles of transmission.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Microbiol Año: 2021 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Microbiol Año: 2021 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Suiza