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COVID-19 PBMCs are doubly harmful, through LDN-mediated lung epithelial damage and monocytic impaired responsiveness to live Pseudomonas aeruginosa exposure.
Gaudin, Clémence; Born-Bony, Maëlys; Villeret, Bérengère; Jaillet, Madeleine; Faille, Dorothée; Timsit, Jean-François; Tran-Dinh, Alexy; Montravers, Philippe; Crestani, Bruno; Garcia-Verdugo, Ignacio; Sallenave, Jean-Michel.
Afiliación
  • Gaudin C; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, Paris, France.
  • Born-Bony M; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, Paris, France.
  • Villeret B; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, Paris, France.
  • Jaillet M; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, Paris, France.
  • Faille D; Université Paris Cité and Université Sorbonne Paris Nord, Inserm, LVTS, Paris, France.
  • Timsit JF; Laboratoire d'Hématologie, AP-HP, Hôpital Bichat, Paris, France.
  • Tran-Dinh A; Réanimation Médicale et des Maladies Infectieuses, Centre Hospitalier Universitaire Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Montravers P; Inserm UMR1148, Laboratory for Vascular Translational Science Bichat Hospital, Paris, France.
  • Crestani B; AP-HP Nord, Anesthesiology and Intensive Care Department, Bichat-Claude Bernard University Hospital, Paris, France.
  • Garcia-Verdugo I; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, Paris, France.
  • Sallenave JM; AP-HP Nord, Anesthesiology and Intensive Care Department, Bichat-Claude Bernard University Hospital, Paris, France.
Front Immunol ; 15: 1398369, 2024.
Article en En | MEDLINE | ID: mdl-38835759
ABSTRACT

Introduction:

Although many studies have underscored the importance of T cells, phenotypically and functionally, fewer have studied the functions of myeloid cells in COVID disease. In particular, the potential role of myeloid cells such as monocytes and low-density neutrophils (LDNs) in innate responses and particular in the defense against secondary bacterial infections has been much less documented.

Methods:

Here, we compared, in a longitudinal study, healthy subjects, idiopathic fibrosis patients, COVID patients who were either hospitalized/moderate (M-) or admitted to ICU (COV-ICU) and patients in ICU hospitalized for other reasons (non-COV-ICU).

Results:

We show that COVID patients have an increased proportion of low-density neutrophils (LDNs), which produce high levels of proteases (particularly, NE, MMP-8 and MMP-9) (unlike non-COV-ICU patients), which are partly responsible for causing type II alveolar cell damage in co-culture experiments. In addition, we showed that M- and ICU-COVID monocytes had reduced responsiveness towards further live Pseudomonas aeruginosa (PAO1 strain) infection, an important pathogen colonizing COVID patients in ICU, as assessed by an impaired secretion of myeloid cytokines (IL-1, TNF, IL-8,…). By contrast, lymphoid cytokines (in particular type 2/type 3) levels remained high, both basally and post PAO1 infection, as reflected by the unimpaired capacity of T cells to proliferate, when stimulated with anti-CD3/CD28 beads.

Discussion:

Overall, our results demonstrate that COVID circulatory T cells have a biased type 2/3 phenotype, unconducive to proper anti-viral responses and that myeloid cells have a dual deleterious phenotype, through their LDN-mediated damaging effect on alveolar cells and their impaired responsiveness (monocyte-mediated) towards bacterial pathogens such as P. aeruginosa.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Infecciones por Pseudomonas / Monocitos / SARS-CoV-2 / COVID-19 / Neutrófilos Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Infecciones por Pseudomonas / Monocitos / SARS-CoV-2 / COVID-19 / Neutrófilos Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Francia