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Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques

The complement system can be viewed as a ‘moderator’ of innate immunity, ‘instructor’ of humoral immunity, and ‘regulator’ of adaptive immunity. While sex and aging are known to affect humoral and cellular immune systems, their impact on the complement pathway in humans and rhesus macaques, a common...

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Autores principales: Kelkar, Natasha S., Goldberg, Benjamin S., Dufloo, Jérémy, Bruel, Timothée, Schwartz, Olivier, Hessell, Ann J., Ackerman, Margaret E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634758/
https://www.ncbi.nlm.nih.gov/pubmed/37961263
http://dx.doi.org/10.1101/2023.10.23.563614
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author Kelkar, Natasha S.
Goldberg, Benjamin S.
Dufloo, Jérémy
Bruel, Timothée
Schwartz, Olivier
Hessell, Ann J.
Ackerman, Margaret E.
author_facet Kelkar, Natasha S.
Goldberg, Benjamin S.
Dufloo, Jérémy
Bruel, Timothée
Schwartz, Olivier
Hessell, Ann J.
Ackerman, Margaret E.
author_sort Kelkar, Natasha S.
collection PubMed
description The complement system can be viewed as a ‘moderator’ of innate immunity, ‘instructor’ of humoral immunity, and ‘regulator’ of adaptive immunity. While sex and aging are known to affect humoral and cellular immune systems, their impact on the complement pathway in humans and rhesus macaques, a commonly used non-human primate model system, have not been well-studied. To address this knowledge gap, we analyzed serum samples from 90 humans and 75 rhesus macaques for the abundance and activity of the complement system components. While sequences of cascade proteins were highly conserved, dramatically different levels were observed between species. Whereas the low levels detected in rhesus samples raised questions about the suitability of the test, differences in levels of complement proteins were observed in male and female humans. Levels of total and antibody-dependent deposition of C1q and C3b on a glycosylated antigen differed between human and rhesus, suggesting differential recognition of glycans. Functional differences in complement-mediated lysis of antibody-sensitized cells were observed in multiple assays and showed that human females frequently exhibited higher lytic activity than human males or rhesus macaques, which typically did not exhibit such sexual dimorphism. Other differences between species and sexes were observed in more narrow contexts—for only certain antibodies, antigens, or assays. Collectively, these results expand our knowledge of sexual dimorphism in the complement system in humans, identifying differences that appear to be absent from rhesus macaques.
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spelling pubmed-106347582023-11-13 Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques Kelkar, Natasha S. Goldberg, Benjamin S. Dufloo, Jérémy Bruel, Timothée Schwartz, Olivier Hessell, Ann J. Ackerman, Margaret E. bioRxiv Article The complement system can be viewed as a ‘moderator’ of innate immunity, ‘instructor’ of humoral immunity, and ‘regulator’ of adaptive immunity. While sex and aging are known to affect humoral and cellular immune systems, their impact on the complement pathway in humans and rhesus macaques, a commonly used non-human primate model system, have not been well-studied. To address this knowledge gap, we analyzed serum samples from 90 humans and 75 rhesus macaques for the abundance and activity of the complement system components. While sequences of cascade proteins were highly conserved, dramatically different levels were observed between species. Whereas the low levels detected in rhesus samples raised questions about the suitability of the test, differences in levels of complement proteins were observed in male and female humans. Levels of total and antibody-dependent deposition of C1q and C3b on a glycosylated antigen differed between human and rhesus, suggesting differential recognition of glycans. Functional differences in complement-mediated lysis of antibody-sensitized cells were observed in multiple assays and showed that human females frequently exhibited higher lytic activity than human males or rhesus macaques, which typically did not exhibit such sexual dimorphism. Other differences between species and sexes were observed in more narrow contexts—for only certain antibodies, antigens, or assays. Collectively, these results expand our knowledge of sexual dimorphism in the complement system in humans, identifying differences that appear to be absent from rhesus macaques. Cold Spring Harbor Laboratory 2023-10-25 /pmc/articles/PMC10634758/ /pubmed/37961263 http://dx.doi.org/10.1101/2023.10.23.563614 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Kelkar, Natasha S.
Goldberg, Benjamin S.
Dufloo, Jérémy
Bruel, Timothée
Schwartz, Olivier
Hessell, Ann J.
Ackerman, Margaret E.
Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques
title Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques
title_full Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques
title_fullStr Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques
title_full_unstemmed Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques
title_short Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques
title_sort sex and species associated differences in complement-mediated immunity in humans and rhesus macaques
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634758/
https://www.ncbi.nlm.nih.gov/pubmed/37961263
http://dx.doi.org/10.1101/2023.10.23.563614
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