Immunomodulatory Effects of Pulmonarom®: In Vitro Induction of TLR and Cytokine Expression in Human Dendritic Cells

Author:

Hernández-Aceves Juan A.1ORCID,Solano-Gálvez Sandra Georgina2,Wilkins-Rodríguez Arturo A.2,Delgado-Domínguez José3ORCID,Lozano Alberto Garcia4ORCID,Cabello-Gutierrez Carlos5ORCID,Huerta Lidia Flor Estela6,Fragoso Gladis1ORCID,Gutiérrez-Kobeh Laila2ORCID,Vázquez-López Rosalino67ORCID

Affiliation:

1. Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Cto. Escolar, C.U., Coyoacán, Mexico City 04510, Mexico

2. Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico

3. Laboratorio de Inmunoparasitología, Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico

4. Laboratorio de Inmunobiología, Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Cto. Escolar S/N, C.U., Coyoacán, Mexico City 04510, Mexico

5. Departamento de Investigación en Virología y Micología, Instituto Nacional de Enfermedades Respiratorias (INER), Calzada de Tlalpan 4502 Belisario Domínguez Tlalpan, Mexico City 14080, Mexico

6. Laboratorio de Farmacología, Escuela Militar de Graduados en Sanidad, Universidad del Ejército y Fuerza Aérea, Secretaría de la Defensa Nacional, Mexico City 11200, Mexico

7. Departamento de Microbiología, Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Norte, Huixquilucan 52786, Mexico

Abstract

Background: Bacterial lysates are known to modulate the immune response against respiratory infections. However, the effects of the commercial bacterial lysate Pulmonarom® on dendritic cells—particularly human monocyte-derived dendritic cells (moDCs)—have not been studied. Additionally, limited data are available on the expression of Toll-like receptors (TLRs) and cytokines following stimulation with bacterial lysates. Methods: Human monocytes were isolated from buffy coats and differentiated into moDCs. Pulmonarom® was lyophilized, quantified, and used to stimulate moDCs. Ultrastructural changes were evaluated using transmission electron microscopy. The expression of TLRs and selected cytokines was analyzed by flow cytometry. Results: Pulmonarom® stimulation induced morphological changes in moDCs, including an increased number of dendrites and lysosomes. It also led to the upregulation of MHC class II molecules and TLRs 2, 3, 6, and 7. Additionally, the production of IL-4, IL-6, IL-8, and MCP-1 was significantly increased. Conclusions: Pulmonarom® promotes moDC maturation, characterized by enhanced antigen presentation capabilities and lysosomal activity, along with increased expression of specific TLRs and cytokines. These features suggest a trained immunity phenotype in moDCs, potentially improving their ability to initiate adaptive immune responses against respiratory pathogens. To our knowledge, this is the first study to investigate the immunomodulatory effects of Pulmonarom® on human moDCs, providing novel insights into its potential as an immunotherapeutic adjuvant.

Funder

Opella, the Sanofi Consumer Healthcare business unit

Publisher

MDPI AG

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