title: Influenza A (H1N1) virus infection triggers severe pulmonary inflammation in lupus-prone mice following viral clearance.
abstract: Each year, up to one fifth of the United States population is infected with influenza virus. Although mortality rates are low, hundreds of thousands are hospitalized each year in the United States. Specific high risk groups, such as those with suppressed or dysregulated immune systems, are at greater danger for influenza complications. Respiratory infections are a common cause of hospitalizations and early mortality in patients with systemic lupus erythematosus (SLE); however, whether this increased infection risk is a consequence of the underlying dysregulated immune background and/or immunosuppressing drugs is unknown. To evaluate the influenza immune response in the context of lupus, as well as assess the effect of infection on autoimmune disease in a controlled setting, we infected lupus-prone MRL/MpJ-Fas(lpr) mice with influenza virus A PR/8/34 H1N1. Interestingly, we found that Fas(lpr) mice generated more influenza A virus specific T cells with less neutrophil accumulation in the lung during acute infection. Moreover, Fas(lpr) mice produced fewer flu-specific IgG and IgM antibodies, but effectively cleared the virus. Further, increased extrinsic apoptosis during influenza infection led to a delay in autoimmune disease pathology with decreased severity of splenomegaly and kidney disease. Following primary influenza A infection, Fas(lpr) mice had severe complications during the contraction and resolution phase with widespread severe pulmonary inflammation. Our findings suggest that influenza infection may not exacerbate autoimmune pathology in mice during acute infection as a direct result of virus induced apoptosis. Additionally, autoimmunity drives an enhanced antigen-specific T cell response to clear the virus, but persisting pulmonary inflammation following viral clearance may cause complications in this lupus animal model.
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Slight-Webb
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
authors.forename: Harini
authors.initials: H
authors.lastname: Bagavant
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
authors.forename: Sherry R
authors.initials: SR
authors.lastname: Crowe
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA; Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. Electronic address: Judith-James@omrf.org.
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007674:Kidney Diseases / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology*; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D011014:Pneumonia / Q000276:immunology* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013163:Splenomegaly / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins
keywords: Influenza; Lupus; MRL-Fas(lpr); Pulmonary inflammation; SLE