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NK Cell and Ig Interplay in Defense against Herpes Simplex Virus Type 1: Epistatic Interaction of CD16A and IgG1 Allotypes of Variable Affinities Modulates Antibody-Dependent Cellular Cytotoxicity and Susceptibility to Clinical Reactivation.
Moraru, Manuela; Black, Laurel E; Muntasell, Aura; Portero, Francisca; López-Botet, Miguel; Reyburn, Hugh T; Pandey, Janardan P; Vilches, Carlos.
Afiliação
  • Moraru M; Inmunogenética e Histocompatibilidad, Instituto de Investigación Sanitaria Puerta de Hierro, 28222 Majadahonda, Madrid, Spain;
  • Black LE; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425;
  • Muntasell A; Institut Hospital del Mar d'Investigaciones Médiques, 08002 Barcelona, Spain;
  • Portero F; Servicio de Microbiología, Instituto de Investigación Sanitaria Puerta de Hierro, 28222 Majadahonda, Madrid, Spain; and.
  • López-Botet M; Institut Hospital del Mar d'Investigaciones Médiques, 08002 Barcelona, Spain;
  • Reyburn HT; Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain.
  • Pandey JP; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425;
  • Vilches C; Inmunogenética e Histocompatibilidad, Instituto de Investigación Sanitaria Puerta de Hierro, 28222 Majadahonda, Madrid, Spain; carlos.vilches@yahoo.com.
J Immunol ; 195(4): 1676-84, 2015 Aug 15.
Article em En | MEDLINE | ID: mdl-26179905
HSV-1 latently infects most humans, causing a variable clinical picture that depends, in part, on host genetic factors. Both IgG and its cellular FcRs, CD16A and CD32A-C (encoded by FCGR3A and FCGR2A-C, respectively, on chromosome 1), display polymorphisms that could affect their defensive function. Of potential relevance are a FCGR3A dimorphism resulting in CD16A-valine/phenylalanine-158 allotypes with different IgG affinity, variations conditioning NK cell expression of CD32B or CD32C, and IgG1 H chain (IGHG1) and kappa-chain (IGKC) polymorphisms determining allotypes designated G1m and Km. In this study, we assessed the contribution of Ig genetic variations and their interaction with FcR polymorphism to HSV-1 susceptibility, as well as their impact on NK cell-mediated Ab-dependent cellular cytotoxicity (ADCC). Our results show an epistatic interaction between IGHG1 and FCGR3A such that the higher affinity CD16A-158V/V genotype associates with an asymptomatic course of HSV-1 infection only in homozygotes for G1m3. Furthermore, CD16A-158V and G1m3 allotypes enhanced ADCC against opsonized HSV-1-infected fibroblasts. Conversely, Km allotypes and CD32B or CD32C expression on NK cells did not significantly influence HSV-1 susceptibility or ADCC. NK cells degranulating against immune serum-opsonized HSV-1-infected fibroblasts had heterogeneous phenotypes. Yet, enhanced ADCC was observed among NK cells showing a differentiated, memory-like phenotype (NKG2C(bright)NKG2A(-)CD57(+)FcRγ(-)), which expand in response to human CMV. These results extend our knowledge on the importance of immunogenetic polymorphisms and NK cell-Ab interplay in the host response against HSV-1 and point to the relevance of interactions between immune responses elicited during chronic coinfection by multiple herpesviruses.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Imunoglobulina G / Células Matadoras Naturais / Herpesvirus Humano 1 / Herpes Simples Limite: Animals / Humans Idioma: En Revista: J Immunol Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Imunoglobulina G / Células Matadoras Naturais / Herpesvirus Humano 1 / Herpes Simples Limite: Animals / Humans Idioma: En Revista: J Immunol Ano de publicação: 2015 Tipo de documento: Article