Influenza viruses are presumed, but not conclusively known, to spread among humans by several possible routes. We provide evidence of a mode of transmission seldom considered for influenza: airborne virus transport on microscopic particles called "aerosolized fomites." In the guinea pig model of influenza virus transmission, we show that the airborne particulates produced by infected animals are mainly non-respiratory in origin. Surprisingly, we find that an uninfected, virus-immune guinea pig whose body is contaminated with influenza virus can transmit the virus through the air to a susceptible partner in a separate cage. We further demonstrate that aerosolized fomites can be generated from inanimate objects, such as by manually rubbing a paper tissue contaminated with influenza virus. Our data suggest that aerosolized fomites may contribute to influenza virus transmission in animal models of human influenza, if not among humans themselves, with important but understudied implications for public health.

The relative and potentially synergistic contributions of genetics and environment to inter-individual immune response variation remain unclear, despite critical implications of such variation in both medicine and evolutionary biology. Here, we quantify interactive effects of genotype and environment on immune traits by investigating different inbred mouse strains rewilded in outdoor enclosures and infected with the parasite, Trichuris muris. Whereas cytokine response heterogeneity was primarily driven by genotype, cellular composition heterogeneity was shaped by interactions between genotype and environment with genetic mediated differences decreasing following rewilding, but less dramatically for T cells than for B cells. Importantly, immune variation was associated with altered parasite burdens. These results indicate that nonheritable influences interact with genetic factors to shape immune variation, with synergistic impacts on the deployment and potential evolution of defense mechanisms.

Animal models are often used to assess the airborne transmissibility of various pathogens, which are typically assumed to be carried by expiratory droplets emitted directly from the respiratory tract of the infected animal. We recently established that influenza virus is also transmissible via “aerosolized fomites,” micron-scale dust particulates released from virus-contaminated surfaces (Asadi et al., Nature Communications, 2020). Here we expand on this observation, by counting and characterizing the particles emitted from guinea pig cages using an Aerodynamic Particle Sizer (APS) and an Interferometric Mie Imaging (IMI) system. Of over 9,000 airborne particles emitted from guinea pig cages and directly imaged with IMI, none had an interference pattern indicative of a liquid droplet. Separate measurements of the particle count using the APS indicate that particle concentrations spike upwards immediately following animal motion, then decay exponentially with a time constant commensurate with the air exchange rate in the cage. Taken together, the results presented here raise the possibility that a non-negligible fraction of airborne influenza transmission events between guinea pigs occurs via aerosolized fomites rather than respiratory droplets, though the relative frequencies of these two routes have yet to be definitively determined.

Animal models are often used to assess the airborne transmissibility of various pathogens, which are typically assumed to be carried by expiratory droplets emitted directly from the respiratory tract of the infected animal. We recently established that influenza virus is also transmissible via “aerosolized fomites,” micron-scale dust particulates released from virus-contaminated surfaces (Asadi et al. in Nat Commun 11(1):4062, 2020). Here we expand on this observation, by counting and characterizing the particles emitted from guinea pig cages using an Aerodynamic Particle Sizer (APS) and an Interferometric Mie Imaging (IMI) system. Of over 9000 airborne particles emitted from guinea pig cages and directly imaged with IMI, none had an interference pattern indicative of a liquid droplet. Separate measurements of the particle count using the APS indicate that particle concentrations spike upwards immediately following animal motion, then decay exponentially with a time constant commensurate with the air exchange rate in the cage. Taken together, the results presented here raise the possibility that a non-negligible fraction of airborne influenza transmission events between guinea pigs occurs via aerosolized fomites rather than respiratory droplets, though the relative frequencies of these two routes have yet to be definitively determined.

Immune responses to pathogens and vaccination can be varied with some individuals inducing optimal responses while others do not. The host genetic profile, environment and previous microbial experience could influence an individual’s response, but the relative contribution, and interactions of these different factors remains largely unknown. Here, using various multi-omics, ecological and single cell approaches, we show that release of genetic inbred strains of mice, 129-SL, PWK and C57/B6 mice, to a rewilded environment and exposure of these rewilded and laboratory specific pathogen free control mice to a helminth parasite, Trichuris muris allowed us to assess the contribution and interaction of host genotype and environment to the immune cell landscape in the blood and secondary lymphoid organs. Critically, we find that the environment has the greatest effect on circulating blood immune cells while the genetic profile has the greatest effect on the mesenteric lymph node. We also observed significant interactions between the host genetic profile, environment, and infection status in their contribution to immune cell composition, with most of the effect driven by the cells of the adaptive immune system. These findings provide a model for contribution and interactions between genetics, environment, and helminth infection in the inter-individual variation of immune responses.

Environmental influences on immune phenotypes are well-documented, but our understanding of which elements of the environment affect immune systems, and how, remains vague. Behaviors, including socializing with others, are central to an individual's interaction with its environment. We tracked behavior of rewilded laboratory mice of three inbred strains in outdoor enclosures and examined contributions of behavior, including social associations, to immune phenotypes. We found that the more associated two individuals were, the more similar their immune phenotypes were. Social association was particularly predictive of similar memory T and B cell profiles and was more influential than sibling relationships or worm infection status. These results highlight the importance of social networks for immune phenotype and reveal important immunological correlates of social life.

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