Nasal Pneumococcal Density is Associated with Microaspiration and Heightened Human Alveolar Macrophage Responsiveness to Bacterial Pathogens.

Mitsi, Elena, Carniel, Beatriz, Reiné, Jesús, Rylance, Jamie ORCID: https://orcid.org/0000-0002-2323-3611, Zaidi, Seher, Soares-Schanoski, Alessandra, Connor, Victoria, Collins, Andrea ORCID: https://orcid.org/0000-0002-4094-1572, Schlitzer, Andreas, Nikolaou, Elissavet, SolorzanoGonzalez, Carla, Pojar, Sherin ORCID: https://orcid.org/0000-0002-7746-3279, Hill, Helen, Hyder-Wright, Angela, Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Oggioni, Marco R, De Ste Croix, Megan, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116, Jochems, Simon ORCID: https://orcid.org/0000-0002-4835-1032 and Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902 (2020) 'Nasal Pneumococcal Density is Associated with Microaspiration and Heightened Human Alveolar Macrophage Responsiveness to Bacterial Pathogens.'. American Journal of Respiratory and Critical Care Medicine, Vol 201, Issue 3, pp. 335-347.

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Abstract

RATIONALE

Pneumococcal pneumonia remains a global health problem. Colonization of the nasopharynx with S.pneumoniae (Spn), although, a prerequisite of infection, is the main source of exposure and immunological boosting in children and adults. However, our knowledge of how nasal colonization impacts on the lung cells, especially on the predominant alveolar macrophage (AM) population, is limited.

OBJECTIVES
Using a Controlled Human Infection Model to achieve nasal colonization with 6B serotype, we investigated the effect of Spn colonization on lung cells.
METHODS
We collected bronchoalveolar lavages from healthy pneumococcal challenged participants aged 18-49 years. Confocal microscopy, molecular and classical microbiology were used to investigate microaspiration and pneumococcal presence in the lower airways. AM opsonophagocytic capacity was assessed by functional assays in vitro, whereas flow cytometry and transcriptomic analysis were used to assess further changes on the lung cellular populations.

MEASUREMENTS AND MAIN RESULTS

AM from Spn-colonized exhibited increased opsonophagocytosis to pneumococcus (11.4% median increase) for four months after clearance of experimental pneumococcal colonization. AM had also increased responses against other bacterial pathogens. Pneumococcal DNA detected in the BAL samples of Spn-colonized were positively correlated with nasal pneumococcal density (r=0.71, p=0.029). Similarly, AM heightened opsonophagocytic capacity was correlated with nasopharyngeal pneumococcal density (r=0.61, p=0.025).
CONCLUSIONS
Our findings demonstrate that nasal colonization with pneumococcus and microaspiration prime AM, leading to brisker responsiveness to both pneumococcus and unrelated bacterial pathogens. The relative abundance of AM in the alveolar spaces, alongside with their potential for non-specific protection, render them an attractive target for novel vaccines. Clinical trial registration available at http://www.isrctn.com, ID: ISRCTN16993271.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Bacteria > QW 138 Enterobacteriaceae WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 202 Pneumonia (General or not elsewhere classified) WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):	https://doi.org/10.1164/rccm.201903-0607OC
Depositing User:	Julie Franco
Date Deposited:	23 Oct 2019 14:47
Last Modified:	17 Aug 2022 08:58
URI:	https://archive.lstmed.ac.uk/id/eprint/12865

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