SUMMARY Homeostatic mucosal immune responses are fine-tuned by naturally evolved interactions with native microbes, and integrating these relationships into experimental models can provide new insights into human diseases. Here, we leverage a murine-adapted airway microbe, Bordetella pseudohinzii ( Bph ), to investigate how chronic colonization impacts mucosal immunity and the development of allergic airway inflammation (AAI). Colonization with Bph induces the differentiation of interleukin-17A (IL-17A)-secreting T-helper cells that aid in controlling bacterial abundance. Bph colonization protects from AAI and is associated with increased production of secretory leukocyte protease inhibitor (SLPI), an antimicrobial peptide with anti-inflammatory properties. These findings are additionally supported by clinical data showing that higher levels of upper respiratory SLPI correlate both with greater asthma control and the presence of Haemophilus, a bacterial genus associated with AAI. We propose that SLPI could be used as a biomarker of beneficial host-commensal relationships in the airway.

The composition of the gut microbiota in early childhood is linked to asthma risk but the role of the gut microbiota in older patients with established asthma is less clear. Here, we used a cohort of 38 school-aged children (19 with asthma) and 57 adults (17 with asthma) to develop a model that aids in the design of mechanistic experiments in gnotobiotic mice. These experiments show that enterotoxigenic Bacteroides fragilis (ETBF) is associated with increased gut permeability, oxidative stress, and markers of Th17-mediated inflammation in the lungs of mice following ovalbumin sensitization and challenge (OSC). Further, ETBF is enriched in a human population with asthma compared to healthy controls. Our results provide evidence that ETBF has the potential to alter the phenotype of airway inflammation in a subset of patients with asthma outside of early childhood which suggests that therapies targeting the gut microbiota may be helpful tools for asthma control.

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BACKGROUND We set out to define the impact of collection, processing, and storage on plasma product microparticle (MP) abundance, potential for nitric oxide (NO) scavenging, and vasoactivity. STUDY DESIGN AND METHODS Three currently US licensed products were tested: liquid plasma (LP), fresh frozen plasma (FFP), and solvent detergent plasma (SDP), along with a product under development, spray‐dried solvent detergent plasma (SD‐SDP) with/without beads. Vasoactivity was assessed in vitro using rabbit aortic vascular rings; MP abundance was determined by flow cytometry; and NO scavenging capacity/rate was determined using a biochemical NO consumption assay. All samples were analyzed unprocessed and following centrifugation at two speeds (2,500× g to remove platelets, and 25,000× g to remove microparticles). RESULTS Significant differences in vasoactivity were observed, with SD‐SDP minus beads demonstrating the greatest constriction and FFP the lowest constriction response. All products exhibited the same total NO scavenging capacity; however, significant differences were observed in the maximal rate of scavenging, with SD‐SDP minus beads and FFP reacting fastest and SDP the slowest. Across all products, platelet and microparticle depletion had no effect on vasoactivity or NO scavenging (total or rate). Microparticles (RBC derived) were found only in FFP and LP, with relative abundance (LP > FFP). Additionally, storage had no effect on total or RBC‐derived MP abundance, NO scavenging, or vasoactivity. CONCLUSION Although vasoactivity differed between plasma products, we did not find similar differences in either total or RBC‐derived MP abundance or NO scavenging capacity/rate.

In the originally published version of this article, due to a data input error, one of the participants in the MARS cohort, participant 0064, was inadvertently categorized as a healthy child in Figure S7 and Tables 1 and S3 instead of as a healthy adult. In addition, in Figures S7C, S7D, and S7E, only a subset of the complete 16S rRNA dataset was shown. The corrected versions of Tables 1 and S3 now appear with the article online. The original and corrected version of Figure S7 appears here. The re-analysis of the corrected dataset does not change the original interpretation of data or conclusions reported in the paper.

There is a widespread assumption that modest chemical modification of a large polymer molecule, by adding a fluorescent label or the like, has no significant effect on polymer solution dynamics. We here report that light tagging of hydroxypropylcellulose (HPC) with fluorescein dye has a significant effect on the dynamic behavior of the chains, as measured using fluorescence photobleaching recovery (FPR) and dynamic light scattering (DLS). We compared unprocessed HPC, HPC processed in preparation for chemical modification, and HPC chemically modified by tagging with a fluorescein moiety. Addition of covalently bound fluorescein to the polymer eliminates the ultraslow (D ≈ 10 −10 cm 2 /s) relaxational mode found with DLS in the unlabeled HPC samples. Our findings explain the perceived discrepancies between DLS and FPR studies of HPC solutions. The discrepancies arise from differences in sample preparation. Comparison of FPR spectra (which measure the single particle diffusion process) and DLS spectra (which measure the relative motions of pairs of particles), each with its own intrinsic time and distance scales, provides insight into the nature of diffusion and the state of dissolution in dilute and nondilute HPC solutions.

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Mucosal immune responses fine-tuned by naturally evolved interactions with native microbes influence airway inflammation but are not routinely integrated into experimental models. Here, we leverage a recently discovered murine-adapted airway microbe, Bordetella pseudohinzii (Bph), to investigate how chronic colonization impacts mucosal immunity and the development of allergic airway inflammation (AAI). Despite the persistent colonization, we did not observe significant weight loss in Bph colonized mice. Microscopic examination of the lungs demonstrated the formation of lymphoid aggregates, consistent with inducible Bronchus Associated Lymphoid Tissue (iBALT). Airway colonization of mice with Bph elicits an antigen-specific Th17 immune response that aids in controlling bacterial abundance. Remarkably, when animals undergo allergic airway challenge, mice previously colonized with Bph demonstrate protection from AAI. This phenotype corresponded to a reduction in type 2 cytokines, eosinophilic infiltration, goblet cell metaplasia, and airway hyper responsiveness. Colonization with Bph does not appear to impact the degree of allergic sensitization nor the presentation of allergen in the lung. Further, colonization and the Th17 response was associated with increased expression of Secreted Leukocyte Proteinase Inhibitor (SLPI), an antimicrobial peptide with anti-inflammatory properties. We confirmed these findings in humans by showing that higher levels of SLPI correlate both to improved asthma control and the presence of the asthma-associated bacterium, Haemophilus influenzae. We propose that SLPI could be used as a biomarker of beneficial host-commensal relationships in the airway.