Biology subjects

Harvill, E. T.

Publications and source records attributed to Harvill, E. T..

3 recordsLinked to original sources

bioRxiv2026

A consortium of human commensals protects against middle ear colonization by otopathogens

A year-long sequencing analysis of bacterial commensals sampled from infants during periods in which they were healthy or suffering recurrent ear infections [otitis media (OM)] identified several species of bacterial commensals that correlate with health and absence of ear infections. Here we consider and test the possibility of a causal relationship between a group of commensals and periods of health. We assemble a set of five health-associated bacterial species into a nasopharyngeal commensal consortium (NPCC) and test whether these organisms can effectively colonize the respiratory tracts of mice so that their effects on invading pathogens could be evaluated. We observed that NPCC efficiently colonize mice and that they provide substantial protection against the otopathogens, Streptococcus pneumoniae and Bordetella pertussis, reducing numbers of each in the middle ears by 99 to 99.9%. The NPCC also affected colonization/growth of these pathogens within the lower respiratory tract, suggesting complexity in these interactions. Together these data demonstrate a profound effect of commensals on invading otopathogens and describe a powerful experimental system in which the important interactions between the healthy infant microbiota and invading pathogens can be studied mechanistically.

microbiology↗

bioRxiv2025

Adult mice with neonatal-like T cell subsets exhibit increased susceptibility to Bordetella pertussis and influenza infection

Infants are significantly more susceptible to respiratory infection, often resulting in increased morbidity and hospitalization, and occasionally death. This susceptibility is partially explained by the developing nature of the thymus in human infants at, and for several months after, birth. However, the contribution of T cells produced in this thymic microenvironment to infant immune responses has received minimal investigation. Here, we utilized a previously described mouse model (Foxn1{Delta}/{Delta}) which exhibits a persistently immature thymus. Through further characterization, we have determined that adult Foxn1{Delta}/{Delta} mice retain some unique T cells observed in neonatal mice including CD8{beta}+ {gamma}{delta} T cells and CD8 T cells displaying a memory-like phenotype. For this reason, we assessed the potential of these neonatal-like T responses to two pathogens which disproportionately affect neonates, Bordetella pertussis (Bp) and influenza. Utilizing these infections, we demonstrate that T cells generated in an incompletely developed thymus fail to control or mount an effective response against Bp. We also observe that Foxn1{Delta}/{Delta} mice control acute influenza infection, a response which does not require IL-17. However, the Foxn1{Delta}/{Delta} mice fail to generate an influenza nucleoprotein (NP) specific CD8+ T cell response which is likely associated with their inability to fully clear the infection. Together, these data suggest that Foxn1{Delta}/{Delta} mice can be utilized to study the generation, function, and persistence of some unique T cells made in a neonatal-like thymus.

immunology↗

bioRxiv2024

A Novel Adhesin of B. pertussis is Key to Colonisation of Epithelial Cells

Despite effective vaccines to protect against Whooping cough, or pertussis, the disease is resurgent in many countries. A switch from acellular to whole-cell vaccines has resulted in waning protective immunity, likely contributing to increases in infection prevalence, underlining the need to better understand B. pertussis virulence. As a respiratory pathogen, B. pertussis colonises the upper respiratory tract utilising an array of adhesins, four of which (FHA, pertactin, Fim2/3) are included in the acellular vaccine. In this study, we identified two Bvg regulated genes that are upregulated during virulence conditions and thus potentially involved in pathogenesis. bp1251 and bp1252 encode orphan toxin B subunits, with homology to AB toxin B subunits. Mutation of bp1251 and bp1252 reduced the in vitro adherence of B. pertussis to A549 and BEAS-2B alveolar and bronchial epithelial-like cells. In a murine model of infection, bp1251 and bp1252 mutant strains were recovered from the nasal cavity and lungs at lower levels than WT. In vitro no effect of mutation of bp1251 or bp1252 on cell invasion or toxicity was found suggesting that these proteins do not form part of a toxin. Given their homology to B subunits of AB toxins, and their role in colonisation, we propose that BP1251 and BP1252 are novel adhesins. Our data suggests that these proteins play a significant role in Bordetella infection and have the potential to further the understanding of B. pertussis pathogenesis.

microbiology↗