The Role Of Chemokines CXCL5 In H1N1 Infection And Its Influence On IBALT Function

Objective Influenza virus is the main cause of human respiratory diseases.The World Health Organization has also identified influenza virus infection as one of the major global public health problems.In recent years,with the discovery of the "memory"function of innate immune cells,the mechanism of action of innate and acquired immunity in pathogen infection inflammation has become a hot spot in the field of host anti-infection.As the key part of innate and acquired immunity in join point,chemokines in arthritic lymphocyte plays an important role in their transfer and recruitment,especially CXCL5 raised parts of inflammation in neutrophils play a key role in the process,so the screening of influenza infection mediated acute lung injury related key protein molecules or cellular control factor,revealing the influenza a virus infection lead to specific molecular mechanism of lung injury,will provide creative potential drug targets for the treatment,the clinical significance,not only will also be small protein molecules for the future research in anti-infection provides important instructions.Method In this study,wild-type WT mice and chemokine CXCL5-/-mice were used as research objects.After anesthesia,the H1N1 influenza strain was infected by nasal drops.The role of the chemokine CXCL5 in H1N1 infection was explored through observation of clinical symptoms,immunohistochemical experiment and ELISA experiment.Then,mass spectrometry was used to screen the prominent immune cell subsets in the lung tissues of mice with CXCL5-/-.Immunofluorescence assay and pathological sections were used to analyze the accumulation characteristics of retained B cells in the lung tissues of WT and CXCL5-/-mice infected with H1N1.Finally,we analyzed the factors of iBALT structure formation in the lung tissues of CXCL5-/-mice through second-generation sequencing technology,and identified the differential genes that promote the formation and maintenance of iBALT structure in CXCL5 deficient mice,laying a foundation for further understanding of the formation and maintenance of iBALT structure.Results:The recruitment of neutrophils in the lung tissues of CXCL5-/-mice significantly decreased after the infection of influenza A H1N1 virus.Neutrophils were the key to solve the primary influenza A virus infection as the "first frontier" of immune cells.In this study,the knockout of CXCL5,a chemokine,reduced the recruitment of neutrophils,but the clearance ability of virus particles in the lung tissues of defective mice increased instead of decreased.We speculated that it might be to resist the infection of influenza virus by regulating the expression of IL-6.At the same time,we found that pulmonary b-cell retention in the lung tissues of CXCL5-/-mice significantly increased,and mainly gathered at the base of bronchial epithelium or around pulmonary vessels,forming a tertiary lymphoid structure-iBALT with distinct T cells and B cell divisions.Found in the validation chemokines CXCL5,bring many regulatory factors such as B cells in the lung tissue chemokine expression of CXCL13 quantity,promote accumulation of B cells in the lung tissue,which creates an easier to form iBALT structure of micro environment,and on the number,size and integrity differs from that of WT mice group,while CXCL5-/-mice iBALT structure of lung tissue formation after flu infection can kick-start local lung immune response against influenza infection.Conclusion The chemokine CXCL5 plays an important role in H1N1 infection,which leads to the formation of a fast-starting tertiary lymphoid tissue iBALT structure in the lung tissue of CXCL5-/-mice.IBALT plays an important role in the body’s resistance to influenza infection.Innovate Induced broncho-associated lymphoid tissue(iBALT)is formed by the body under the stimulation of pathogen infection or inflammation and other factors.It is generally distributed near the base of bronchial epithelium or around pulmonary vessels,and there are obvious T cells and B cells in it,including stromal cells,lymphoid vessels and high endothelial venules.It has been reported that iBALT plays an important role in lung infection,interstitial lung disease,non-small cell lung cancer and other diseases and may be related to its pathogenesis.IBALT is a tertiary lymphoid tissue similar to the secondary lymphoid organ in structure.It has been proven to initiate a similar natural immune response and then regulate the adaptive immune process.However,iBALT has two sides.It can also exacerbate local tissue damage in autoimmune diseases.At present,the mechanism of iBALT formation induced by pulmonary infection or chronic inflammation and the key factors to maintain the presence of iBALT are still unclear.