Intradermal immunization with wall teichoic acid (WTA) elicits and augments an anti-WTA IgG response that protects mice from methicillin-resistant Staphylococcus aureus infection independent of mannose-binding lectin status.
The objectives of this study were to investigate the immune response to intradermal immunization with wall teichoic acid (WTA) and the effect of MBL deficiency in a murine model of infection with methicillin-resistant Staphylococcus aureus (MRSA). WTA is a bacterial cell wall component that is implicated in invasive infection. We tested susceptibility to MRSA infection in wild type (WT) and MBL deficient mice using two strains of MRSA: MW2, a community-associated MRSA (CA-MRSA); and COL, a healthcare-associated MRSA (HA-MRSA). We also performed in vitro assays to investigate the effects of anti-WTA IgG containing murine serum on complement activation and bacterial growth in whole blood. We found that MBL knockout (KO) mice are relatively resistant to a specific MRSA strain, MW2 CA-MRSA, compared to WT mice, while both strains of mice had similar susceptibility to a different strain, COL HA-MRSA. Intradermal immunization with WTA elicited and augmented an anti-WTA IgG response in both WT and MBL KO mice. WTA immunization significantly reduced susceptibility to both MW2 CA-MRSA and COL HA-MRSA, independent of the presence of MBL. The protective mechanisms of anti-WTA IgG are mediated at least in part by complement activation and clearance of bacteria from blood. The significance of these findings is that 1) Intradermal immunization with WTA induces production of anti-WTA IgG; and 2) This anti-WTA IgG response protects from infection with both MW2 CA-MRSA and COL HA-MRSA even in the absence of MBL, the deficiency of which is common in humans.
Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. ktakahashi1@partners.org
Kazue
K
Takahashi
Kenji
K
Kurokawa
Patience
P
Moyo
Dong-Jun
DJ
Jung
Jang-Hyun
JH
An
Lorencia
L
Chigweshe
Elahna
E
Paul
Bok Luel
BL
Lee
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000276:immunology*; D003167:Complement Activation; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007271:Injections, Intradermal; D037601:Mannose-Binding Lectin / Q000172:deficiency; D037241:Mannose-Binding Lectins / Q000502:physiology*; D008661:Metabolism, Inborn Errors; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D013682:Teichoic Acids / Q000276:immunology / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D037601:Mannose-Binding Lectin; D037241:Mannose-Binding Lectins; D013682:Teichoic Acids; C048844:anti-IgG