title: Sortase A induces Th17-mediated and antibody-independent immunity to heterologous serotypes of group A streptococci.
abstract: Group A streptococci (GAS) are associated with a variety of mucosal and invasive human infections. Recurrent infections by highly heterologous serotypes indicate that cross-serotype immunity is critical for prevention of GAS infections; however, mechanisms underlying serotype-independent protection are poorly understood. Here we report that intranasal vaccination of mice with Sortase A (SrtA), a conserved cell wall bound protein, reduced colonization of nasal-associated lymphoid tissue (NALT) by heterologous serotypes of GAS. Vaccination significantly increased CD4+ IL-17A+ cells in NALT and depletion of IL-17A by neutralizing antibody prevented GAS clearance from NALT which was dependent on immunization with SrtA. Vaccination also induced high levels of SrtA-specific antibodies; however, immunized, B cell-deficient mice cleared streptococcal challenges as efficiently as wild type mice, indicating that the cross-serotype protection is Th17-biased and antibody-independent. Furthermore, efficient GAS clearance from NALT was associated with a rapid neutrophil influx into NALT of immunized mice. These results suggest that serotype independent immune protection against GAS mucosal infection can be achieved by intranasal vaccination with SrtA and enhanced neutrophil function is critical for anti-GAS defense and might be a target for prevention of GAS infections.
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing, China.
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing, China.
authors.forename: Honglian
authors.initials: H
authors.lastname: Cui
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Baidong
authors.initials: B
authors.lastname: Hou
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Paul Patrick
authors.initials: PP
authors.lastname: Cleary
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing, China.
authors.forename: Beinan
authors.initials: B
authors.lastname: Wang
mesh_terms: D000281:Administration, Intranasal; D019881:Aminoacyltransferases / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013290:Streptococcal Infections / Q000276:immunology* / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology / Q000637:transplantation; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D018941:Antigens, CD19; D001426:Bacterial Proteins; C098680:Il17a protein, mouse; D020381:Interleukin-17; D022541:Streptococcal Vaccines; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases