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https://www.arca.fiocruz.br/handle/icict/30656
IN SITU IMMUNE SIGNATURES AND MICROBIAL LOAD AT THE NASOPHARYNGEAL INTERFACE IN CHILDREN WITH ACUTE RESPIRATORY INFECTION
IRA
Resposta imune
nContador
Iinterferon
Carga viral
imunidade inata
Imunidade adaptativa
ARI
Immune response
nCounter
Interferon
Viral load
Innate immunity
Adaptive immunity
Autor(es)
Afiliação
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Federal University of Bahia. School of Medicine. Salvador, BA, Brazil / Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
University of São Paulo. School of Pharmaceutical Sciences. Department of Clinical and Toxicological Analyses. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Federal University of Bahia. School of Medicine. Salvador, BA, Brazil / Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
University of São Paulo. School of Pharmaceutical Sciences. Department of Clinical and Toxicological Analyses. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pediatrics. Salvador, BA, Brazil.
Resumo em Inglês
Acute respiratory infection (ARI) is the most frequent cause for hospitalization in infants and young children. Using multiplexed nCounter technology to digitally quantify 600 human mRNAs in parallel with 14 virus- and 5 bacterium-specific RNAs, we characterized viral and bacterial presence in nasopharyngeal aspirates (NPA) of 58 children with ARI and determined the corresponding in situ immune profiles. NPA contained different groups of organisms and these were classified into bacterial (n = 27), viral (n = 5), codetection [containing both viral and bacterial transcripts (n = 21), or indeterminate intermediate where microbial load is below threshold (n = 5)]. We then identified differentially expressed immune transcripts (DEITs) comparing NPAs from symptomatic children vs. healthy controls, and comparing children presenting NPAs with detectable microbial load vs. indeterminate. We observed a strong innate immune response in NPAs, due to the presence of evolutionarily conserved type I Interferon (IFN)-stimulated genes (ISG), which was correlated with total bacterial and/or viral load. In comparison with indeterminate NPAs, adaptive immunity transcripts discriminated among viral, bacterial, and codetected microbial profiles. In viral NPAs, B cell transcripts were significantly enriched among DEITs, while only type III IFN was correlated with viral load. In bacterial NPAs, myeloid cells and coinhibitory transcripts were enriched and significantly correlated with bacterial load. In conclusion, digital nCounter transcriptomics provide a microbial and immunological in situ "snapshot" of the nasopharyngeal interface in children with ARI. This enabled discrimination among viral, bacterial, codetection, and indeterminate transcripts in the samples using non-invasive sampling.
Palavras-chave
Análise de redesIRA
Resposta imune
nContador
Iinterferon
Carga viral
imunidade inata
Imunidade adaptativa
Palavras-chave em inglês
Network analysisARI
Immune response
nCounter
Interferon
Viral load
Innate immunity
Adaptive immunity
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