How the Neuropeptide CGRP Helps Bacteria Evade Newborn Immune Defenses in Pneumonia | Research

The takeaway

CGRP — the same peptide targeted by migraine drugs — suppresses protective neutrophil activation in neonatal lungs, allowing Group B Streptococcus to evade immune clearance and worsen pneumonia.

Bacteria exploit CGRP to evade immunity
Group B Streptococcus co-opts the neuropeptide CGRP to suppress the development of bacteria-killing SiglecFhi neutrophils in neonatal lungs, worsening pneumonia severity.

What the researchers found

In a neonatal mouse model of GBS pneumonia, neutrophils were recruited to infected lungs but their phenotype differed based on disease severity. Pups with moderate disease developed SiglecFhi neutrophils — a phenotype with enhanced phagocytic capacity and superior bacterial clearance. Pups with severe disease failed to develop this protective neutrophil type.

The key difference was CGRP: severely affected pups showed increased CGRP expression in the lungs. CGRP directly suppressed neutrophil activation into the SiglecFhi phenotype, limiting their antibacterial function. This represents a neuroimmune axis that GBS exploits to evade host immunity — the bacteria essentially co-opt a neural signaling molecule to shut down the most effective form of immune defense.

Why it matters

Neonatal GBS infection is a leading cause of newborn mortality worldwide. Understanding why some babies develop severe disease while others fight off the infection is critical for developing better treatments. This study identifies CGRP as a key immunosuppressive factor — and since CGRP-blocking drugs already exist (they're used for migraines), there's an immediate therapeutic hypothesis: could CGRP antagonists help newborns fight GBS pneumonia?

How the study worked

Researchers used a clinically relevant neonatal mouse model of GBS pneumonia. Immune cell infiltration and phenotyping (including SiglecF expression on neutrophils) were analyzed in infected neonatal lungs using flow cytometry. Disease severity was correlated with neutrophil phenotype and CGRP expression levels. The direct effect of CGRP on neutrophil activation was tested to establish the mechanistic link between CGRP levels and suppressed SiglecFhi development.

What this study cannot tell us

This is a mouse model study, and neonatal immune responses differ significantly between mice and human newborns. Whether CGRP plays the same immunosuppressive role in human neonatal GBS infection is unknown. The study did not test whether CGRP-blocking drugs could improve outcomes in the infection model. The mechanisms by which GBS triggers increased CGRP production in the lungs were not fully elucidated. Sample sizes for the neonatal mouse experiments were not reported in the abstract.

How to read the evidence

This is a preclinical mechanistic study using a neonatal mouse model. The evidence for the CGRP-neutrophil suppression mechanism is compelling within the mouse model, but clinical relevance to human neonates remains to be established.

When this study was published

Published in 2025, this is a very recent study at the forefront of neuroimmunology research, revealing novel roles for CGRP in neonatal infection.

The bigger picture

The neuroimmune axis — crosstalk between the nervous system and immune system — is one of the hottest areas in biomedical research. CGRP is increasingly recognized as a dual-function peptide: it causes vasodilation and pain signaling (hence its role in migraine) but also modulates immune responses. This study reveals a dark side of CGRP in neonatal immunity, adding to evidence that pathogens can exploit neuroimmune crosstalk to evade host defenses. The fact that CGRP-blocking drugs are already FDA-approved for migraine opens an intriguing therapeutic avenue.

Questions still open

Could CGRP-blocking drugs (already approved for migraine) be repurposed to improve outcomes in neonatal GBS pneumonia?
Does GBS actively stimulate CGRP release from lung sensory neurons, or is CGRP elevation a bystander effect of infection-induced inflammation?
Is CGRP-mediated neutrophil suppression specific to neonates, or does it also occur in adult pneumonia?

Common questions

What does CGRP have to do with newborn infections?

CGRP is a neuropeptide normally involved in pain signaling and blood vessel dilation (it's the target of migraine drugs). This study found that in neonatal pneumonia, CGRP is produced in excess in the lungs and suppresses the most effective form of infection-fighting white blood cells. This allows bacteria to survive and the infection to worsen.

Could migraine drugs help fight newborn infections?

It's a fascinating hypothesis. CGRP-blocking antibodies already approved for migraine could theoretically restore immune cell function in infected neonatal lungs. However, this has only been shown in mice, and using these drugs in human newborns would require extensive safety testing and clinical trials.

Read the original research

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

Microorganisms, 13(9)

View on PubMed ↗Publisher’s paper ↗

Citation

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. (2025). CGRP Suppresses Protective SiglecFhi Neutrophil Development in Neonatal Group B Streptococcus Pneumonia.. Microorganisms, 13(9). https://doi.org/10.3390/microorganisms13092119