Highlights d Nociceptors mediate enteric defense against Salmonella colonization and PP invasion d Nociceptors shape the gut microbiota and SFB levels to resist Salmonella infection d Nociceptors suppress M cell density to regulate SFB and limit bacterial invasion d Nociceptors directly sense Salmonella to release CGRP to promote host defense

Newborn screening (NBS) for severe combined immunodeficiency (SCID) utilizing Tcell receptor excision circles (TRECs) has been implemented in all 50 states as of December 2018 and has been transformative for the clinical care of SCID patients.Though having high sensitivity for SCID, NBS-SCID has low specificity, therefore is able to detect other causes of lymphopenia in newborns including many inborn errors of immunity (IEIs). In a recent study, three of six newborns later diagnosed with Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome were found to have a low TRECs and lymphopenia at birth. This presents an opportunity to increase the detection and diagnosis of WHIM syndrome by NBS-SCID with immunological follow-up along with a combination of flow cytometry for immune cell subsets, absolute neutrophil count, and genetic testing, extending beyond the conventional bone marrow studies. Coupled with emerging technologies such as nextgeneration sequencing, transcriptomics and proteomics, dried blood spots used in NBS-SCID will promote earlier detection, diagnosis, and therefore treatment of IEIs such as WHIM syndrome.

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