CGRP Suppresses Protective SiglecFhi Neutrophil Development in Neonatal Group B Streptococcus Pneumonia

Lorga, Inês; Teixeira, Ana Sofia; Carvalho, Bárbara; Soares, Joana; Ribeiro, Nuno; Cardoso, Marcos S.; Cunha, Joana; Santos, Joana; Silva, Regina A.; Vilanova, Manuel; Bonifácio Andrade, Elva

doi:10.3390/microorganisms13092119

Open AccessArticle

CGRP Suppresses Protective SiglecF^hi Neutrophil Development in Neonatal Group B Streptococcus Pneumonia

by

Inês Lorga

^1,2,†

,

Ana Sofia Teixeira

^2,†

,

Bárbara Carvalho

^3,4,

Joana Soares

²,

Nuno Ribeiro

^1,2,

Marcos S. Cardoso

^2,3,

Joana Cunha

^3,4,5

,

Joana Santos

^3,4,5,

Regina A. Silva

^3,4,6,

Manuel Vilanova

^1,2 and

Elva Bonifácio Andrade

^1,2,3,4,*

¹

ICBAS—School of Medicine and Biomedical Sciences, Universidade do Porto, 4050-313 Porto, Portugal

²

i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal

³

E2S—Escola Superior de Saúde, Instituto Politécnico do Porto, 4200-072 Porto, Portugal

⁴

Área Técnico-Científica Anatomia Patológica, Citológica e Tanatológica, Escola Superior de Saúde, Instituto Politécnico do Porto, 4200-072 Porto, Portugal

⁵

Serviço de Anatomia Patológica, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, 4464-513 Matosinhos, Portugal

⁶

REQUIMTE/LAQV, Escola Superior de Saúde, Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Microorganisms 2025, 13(9), 2119; https://doi.org/10.3390/microorganisms13092119

Submission received: 7 August 2025 / Revised: 29 August 2025 / Accepted: 3 September 2025 / Published: 11 September 2025

(This article belongs to the Section Molecular Microbiology and Immunology)

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Abstract

Neonatal pneumonia, a leading cause of morbidity and mortality, is frequently caused by Group B Streptococcus (GBS). The mechanisms underlying protective immunity to this pathogen in the neonatal lung remain incompletely understood. Using a clinically relevant neonatal mouse model of GBS pneumonia, we investigated the immune mechanisms influencing disease severity. We demonstrate that neutrophils are effectively recruited to the lungs of infected neonates, but their phenotype differs with disease severity. In pups with moderate disease, we observe significant infiltration of SiglecF^hi neutrophils, a phenotype associated with enhanced phagocytic capacity and bacterial clearance. In contrast, pups with severe disease failed to develop SiglecF^hi neutrophils, resulting in reduced bacterial clearance and worsened pathology. We further show that severity is associated with increased expression of calcitonin gene-related peptide (CGRP) in the lungs. CGRP suppressed neutrophil activation into the SiglecF^hi phenotype, thereby limiting their antibacterial function. Our findings show that GBS exploits the neuroimmune axis to evade host immunity through CGRP-mediated suppression of neutrophil activation.

Keywords: Group B Streptococcus; neonatal immunity; innate immunity; pneumonia; lung; neutrophil; SiglecF; CGRP

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MDPI and ACS Style

Lorga, I.; Teixeira, A.S.; Carvalho, B.; Soares, J.; Ribeiro, N.; Cardoso, M.S.; Cunha, J.; Santos, J.; Silva, R.A.; Vilanova, M.; et al. CGRP Suppresses Protective SiglecF^hi Neutrophil Development in Neonatal Group B Streptococcus Pneumonia. Microorganisms 2025, 13, 2119. https://doi.org/10.3390/microorganisms13092119

AMA Style

Lorga I, Teixeira AS, Carvalho B, Soares J, Ribeiro N, Cardoso MS, Cunha J, Santos J, Silva RA, Vilanova M, et al. CGRP Suppresses Protective SiglecF^hi Neutrophil Development in Neonatal Group B Streptococcus Pneumonia. Microorganisms. 2025; 13(9):2119. https://doi.org/10.3390/microorganisms13092119

Chicago/Turabian Style

Lorga, Inês, Ana Sofia Teixeira, Bárbara Carvalho, Joana Soares, Nuno Ribeiro, Marcos S. Cardoso, Joana Cunha, Joana Santos, Regina A. Silva, Manuel Vilanova, and et al. 2025. "CGRP Suppresses Protective SiglecF^hi Neutrophil Development in Neonatal Group B Streptococcus Pneumonia" Microorganisms 13, no. 9: 2119. https://doi.org/10.3390/microorganisms13092119

APA Style

Lorga, I., Teixeira, A. S., Carvalho, B., Soares, J., Ribeiro, N., Cardoso, M. S., Cunha, J., Santos, J., Silva, R. A., Vilanova, M., & Bonifácio Andrade, E. (2025). CGRP Suppresses Protective SiglecF^hi Neutrophil Development in Neonatal Group B Streptococcus Pneumonia. Microorganisms, 13(9), 2119. https://doi.org/10.3390/microorganisms13092119

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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CGRP Suppresses Protective SiglecF^hi Neutrophil Development in Neonatal Group B Streptococcus Pneumonia

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