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Maternal HIV status skews transcriptomic response in infant cord blood monocytes exposed to Bacillus Calmette--Guerín
- Source :
- AIDS. 35:23-32
- Publication Year :
- 2020
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2020.
-
Abstract
- OBJECTIVES HIV-exposed uninfected (HEU) infants exhibit altered vaccine responses and an increased mortality compared with HIV-unexposed infants. Here, vaccine responses in HEU and HIV-unexposed cord blood monocytes (CBMs) were assessed following Bacillus Calmette--Guerin (BCG) treatment. DESIGN Innate responses to in-vitro BCG treatment were assessed through transcriptional profiling using CBMs obtained from a Nigerian cohort of HIV-infected and uninfected women. METHODS HIV-unexposed (n = 9) and HEU (n = 10) infant CBMs were treated with BCG and transcriptionally profiled with the Nanostring nCounter platform. Differential expression and pathway enrichment analyses were performed, and transcripts were identified with enhanced or dampened BCG responses. RESULTS Following BCG stimulation, several pathways associated with inflammatory gene expression were upregulated irrespective of HIV exposure status. Both HIV-unexposed and HEU monocytes increased expression of several cytokines characteristic of innate BCG responses, including IL1β, TNFα, and IL-6. Using differential expression analysis, we identified genes significantly upregulated in HEU compared with HIV-unexposed monocytes including monocyte chemokine CCL7 and anti-inflammatory cytokine TNFAIP6. In contrast, genes significantly upregulated in HIV-unexposed compared with HEU monocytes include chemokine CCL3 and cytokine IL23A, both of which influence anti-mycobacterial T-cell responses. Finally, two genes, which regulate prostaglandin production, CSF2 and PTGS2, were also more significantly upregulated in the HIV-unexposed cord blood indicating that inflammatory mediators are suppressed in the HEU infants. CONCLUSION HEU monocytes exhibit altered induction of several key innate immune responses, providing mechanistic insights into dysregulated innate response pathways that can be therapeutically targeted to improve vaccine responses in HEU infants.
- Subjects :
- 0301 basic medicine
Chemokine
Innate immune system
biology
business.industry
medicine.medical_treatment
Monocyte
Immunology
CCL3
Transcriptome
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Infectious Diseases
Cytokine
medicine.anatomical_structure
Cord blood
biology.protein
Immunology and Allergy
Medicine
Tumor necrosis factor alpha
030212 general & internal medicine
business
Subjects
Details
- ISSN :
- 14735571 and 02699370
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- AIDS
- Accession number :
- edsair.doi...........6f1da202a8d913144f9a1dc10705089f
- Full Text :
- https://doi.org/10.1097/qad.0000000000002706