Most viruses first encounter host cells at mucosal surfaces, which are typically colonized by a complex a vast range of commensals and potential pathogenic bacteria, which form a complex microbial community. This community is assumed to be constantly subject to synergistic and competitive interspecies interactions. Disturbances in the equilibrium, for instance due to the acquisition of new bacteria or viruses, may lead to overgrowth and invasion. While evidence suggests potential antagonistic effects where the bacterial microbiome protects the host from viral infection, increasing evidences highlights the severe pathogenicity occurring as a consequence of virus-bacteria interactions in areas inhabited by normally benign members of the native microflora. The immune system may also be involved in this competition, as one viral species might have few escape strategies to evade the immune system and therefore may use co-inhabitants to survive, whereas the reverse phenomenon (i.e. one species may trigger the immune system to combat the other species) may also occur. A better understanding of the impact of virus-bacteria on the mucosal immune response may provide better insight into the pathogenesis of different acute or chronic disease settings.
The mucosal surfaces of the body are designed to provide resistance to microbial infection. They are also home to complex microbial ecosystems characterized by a vast range of commensals and potential pathogenic bacteria and viruses. This community is assumed to be constantly subject to synergistic and competitive interspecies interactions. Disturbances in the equilibrium, for instance due to the acquisition of new bacteria or viruses, may lead to overgrowth and invasion. Higher organisms have evolved a unique mucosal immune system, that interacts with the commensal and pathogenic microorganisms, mainly represented by viruses and bacteria, to promote health as well as protect the vast mucosal surfaces of the body which include the gut, the skin, nasal and oral cavities and the ano-genital tract. It is intuitive that the mucosal surfaces represent a fragile interface between the immune system and the microbiological environment. Indeed, in order to maintain local homeostasis, the innate and adaptive immune system must continuously discriminate between innocuous antigens and those associated with microbial pathogens. As our understanding grows, polymicrobial interactions move from the exception to the norm, and now it appears evident that viruses and bacteria are no longer mutually exclusive disease-causing agents. While evidence suggests potential antagonistic effects where the bacterial species protects the host from viral infection, the increased pathogenicity occurring as a consequence of virus-bacteria interactions in areas inhabited by normally benign members of the native microflora are emerging as a critical public health issue. Viruses can utilizing bacterial components to enter target cells, while bacteria can capitalize on the destructive nature of virus replication to gain footholds into previously inaccessible regions. Throughout the body these microorganisms can collaborate to better each other, to the detriment of the host. Any breakdown on this complex polymicrobial interactions and their influence on immune discrimination process can potentially lead to a severe inflammatory disease. However, very little is known about host immune responses to polymicrobial infections. It is clear that immune responses against bacteria or viruses alone are dissimilar (Allard et al., 2009), but whether dual infection stimulates both immune pathways or is dominated by one has only recently been explored. The mechanisms employed by the mucosal immune system to maintain this delicate balance are many and varied, and a comprehensive understanding of how they collectively operate would provide novel insight into a wide variety of acute and chronic diseases. Thus, further elucidation and discovery of virus-bacteria relationships and mechanisms involved in infection is crucial. Although technically challenging, such advancement may in part achieved by the integration of flow cytometry platforms to traditional and/or NGS technologies. Then, this project arises from the need to acquire a new flow cytometry platform, which will be independently and flexibly used for a variety of applications, focusing on virus-bacterial interactions in different clinical settings. In particular, we plan to understand the dynamics between commensals and pathogens in the respiratory, gastrointestinal and genital tracts in order to provide better insight into the pathogenesis of several acute and chronic diseases. In particular, the impact of polymicrobial infections on mucosal immunity will be evaluated during respiratory viral infections (e.g. respiratory syncytial virus, human rhinovirus, influenza virus) in infants, in elderly patients and those with hematological malignancies admitted to an intensive care unit of Policlinico Umberto Hospital. A part of the project will be dedicated to unraveling the role of polymicrobial interactions on shaping immune response in fibrosis cystic, oral and ano-genital HPV infection. The relationship between HIV infection and the gastrointestinal immune system will be also analyzed. The main innovation aspects of this project are to understanding whether polymicrobial communities are highly individualized to each patient and promote intricate inter-microbial and host pathogen interactions, which might alter the mucosal immunity and direct the course of disease.