Defective Monocyte Enzymatic Function and an Inhibitory Immune Phenotype in Human Immunodeficiency Virus-Exposed Uninfected African Infants in the Era of Antiretroviral Therapy.
HIV-exposed uninfected, human herpes virus', vaccine responses, Heamophilus influenzae type b, monocytes
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
28 09 2022
28 09 2022
Historique:
received:
22
09
2021
accepted:
07
04
2022
pubmed:
12
4
2022
medline:
1
10
2022
entrez:
11
4
2022
Statut:
ppublish
Résumé
Human immunodeficiency virus-exposed uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated whether human immunodeficiency virus (HIV)-exposure dysregulates HEU immunity, vaccine-antibody production, and human herpes virus amplify this effect. Thirty-four HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort and observed up to 6 weeks of age; and then a subsequent 43 HIV-infected and 61 HIV-uninfected mother-infant pairs were recruited into a longitudinal infant cohort at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HIV-unexposed uninfected (HU) infants. We demonstrate (1) altered monocyte phagosomal function and B-cell subset homeostasis and (2) lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-tetanus toxoid immunoglobulin G titers in HEU compared with HU infants. Human herpes virus infection was similar between HEU and HU infants. In the era of antiretroviral therapy-mediated viral suppression, HIV exposure may dysregulate monocyte and B-cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.
Sections du résumé
BACKGROUND
Human immunodeficiency virus-exposed uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated whether human immunodeficiency virus (HIV)-exposure dysregulates HEU immunity, vaccine-antibody production, and human herpes virus amplify this effect.
METHODS
Thirty-four HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort and observed up to 6 weeks of age; and then a subsequent 43 HIV-infected and 61 HIV-uninfected mother-infant pairs were recruited into a longitudinal infant cohort at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HIV-unexposed uninfected (HU) infants.
RESULTS
We demonstrate (1) altered monocyte phagosomal function and B-cell subset homeostasis and (2) lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-tetanus toxoid immunoglobulin G titers in HEU compared with HU infants. Human herpes virus infection was similar between HEU and HU infants.
CONCLUSIONS
In the era of antiretroviral therapy-mediated viral suppression, HIV exposure may dysregulate monocyte and B-cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.
Identifiants
pubmed: 35403683
pii: 6566242
doi: 10.1093/infdis/jiac133
pmc: PMC9518837
doi:
Substances chimiques
Immunoglobulin G
0
Tetanus Toxoid
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1243-1255Subventions
Organisme : Medical Research Council
ID : MR/P020526/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Déclaration de conflit d'intérêts
Potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Références
Science. 2016 Apr 22;352(6284):aaf1098
pubmed: 27102489
Clin Vaccine Immunol. 2016 Jul 05;23(7):576-85
pubmed: 27170641
Lancet Glob Health. 2020 Jan;8(1):e67-e75
pubmed: 31791800
JAMA. 2011 Feb 9;305(6):576-84
pubmed: 21304083
J Infect Dis. 2017 Feb 1;215(3):415-419
pubmed: 27932617
Front Immunol. 2019 Mar 26;10:595
pubmed: 30972079
Mucosal Immunol. 2014 Sep;7(5):1116-26
pubmed: 24472847
Front Immunol. 2017 Sep 28;8:1222
pubmed: 29033941
Curr Opin Microbiol. 2002 Feb;5(1):56-61
pubmed: 11834370
Sci Rep. 2017 Apr 26;7(1):1209
pubmed: 28446770
Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19436-41
pubmed: 17158796
Open Forum Infect Dis. 2019 May 20;6(6):ofz237
pubmed: 31214627
J Clin Invest. 2011 Jul;121(7):2614-24
pubmed: 21633172
Pediatr Infect Dis J. 2018 Apr;37(4):304-309
pubmed: 29140938
Sci Rep. 2017 Oct 23;7(1):13820
pubmed: 29062060
PLoS One. 2006 Dec 20;1:e102
pubmed: 17183635
J Med Virol. 1992 Nov;38(3):183-90
pubmed: 1287131
Clin Infect Dis. 2021 Mar 15;72(6):1026-1032
pubmed: 32067040
Clin Infect Dis. 2019 Mar 19;68(7):1193-1203
pubmed: 30215689
PLoS One. 2015 Aug 18;10(8):e0135375
pubmed: 26284528
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2262-7
pubmed: 16461915
Front Immunol. 2017 Sep 06;8:1060
pubmed: 28932223
Brain Behav Immun. 2021 Jan;91:65-73
pubmed: 32860940
Clin Infect Dis. 2020 Dec 31;71(11):2858-2868
pubmed: 31832638
Front Immunol. 2016 May 23;7:199
pubmed: 27242802
Eur J Immunol. 1990 May;20(5):1085-9
pubmed: 2113474
Immunol Rev. 2013 Jul;254(1):207-24
pubmed: 23772622
Sci Rep. 2019 Dec 2;9(1):18124
pubmed: 31792230
Front Immunol. 2016 Nov 16;7:505
pubmed: 27899925
Clin Exp Immunol. 2014 Apr;176(1):11-22
pubmed: 24325737
Blood. 2007 Mar 1;109(5):2086-8
pubmed: 17053062
AIDS. 2015 Jan 14;29(2):155-65
pubmed: 25535752
AIDS. 2014 May 15;28(8):1115-24
pubmed: 24752082
J Acquir Immune Defic Syndr. 2019 Sep 1;82(1):1-8
pubmed: 31408450
BMC Pediatr. 2020 Apr 23;20(1):181
pubmed: 32326903
Immunology. 2010 Mar;129(3):446-54
pubmed: 20002789
AIDS. 2013 Jan 14;27(2):175-80
pubmed: 23135171
PLoS Pathog. 2016 Jan 14;12(1):e1005368
pubmed: 26766566
Expert Rev Vaccines. 2019 Jan;18(1):95-104
pubmed: 30417710
Clin Vaccine Immunol. 2011 Sep;18(9):1406-9
pubmed: 21775515
AIDS. 2017 Aug 24;31(13):1809-1818
pubmed: 28609400
Lancet Child Adolesc Health. 2020 Mar;4(3):220-231
pubmed: 31932246
Clin Vaccine Immunol. 2014 Dec;21(12):1661-7
pubmed: 25298109
Methods. 2006 Apr;38(4):274-82
pubmed: 16473524
J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):245-255
pubmed: 24732876