Dataset Information

Maternal HIV status skews transcriptomic response in infant cord blood monocytes exposed to Bacillus Calmette--Guerin.

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--Guerín (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.

SUBMITTER: Jones CI

PROVIDER: S-EPMC7718394 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThe Bacillus Calmette-Guerin (BCG) vaccine has been in use for 99 years, and is regarded as one of the oldest human vaccines known today. It is recommended primarily due to its effect in preventing the most severe forms of tuberculosis, including disseminated tuberculosis and meningeal tuberculosis in children; however, its efficacy in preventing pulmonary tuberculosis and TB reactivation in adults has been questioned. Several studies however have found that asides from its role in tuberculosis prevention, the BCG vaccine also has protective effects against a host of other viral infections in humans, an effect which has been termed: heterologous, non-specific or off-target.ObjectivesAs we approach 100 years since the discovery of the BCG vaccine, we review the evidence of the non-specific protection offered by the vaccine against viral infections, discuss the possible mechanisms of action of these effects, highlight the implications these effects could have on vaccinology and summarize the recent epidemiological correlation between the vaccine and the on-going COVID-19 pandemic.ResultsSeveral epidemiological studies have established that BCG does reduce all-cause mortality in infants, and also the time of vaccination influences this effect significantly. This effect has been attributed to the protective effect of the vaccine in preventing unrelated viral infections during the neonatal period. Some of such viral infections that have been investigated include: herpes simplex virus (HSV), human Papilloma virus (HPV), yellow fever virus (YFV), respiratory syncytial virus (RSV) and influenza virus type A (H1N1). These effects are thought to be mediated via induction of innate immune memory as well as heterologous lymphocytic activation. While epidemiological studies have suggested a correlation, the potential protection of the BCG vaccine against COVID-19 transmission and mortality rates is currently unclear. Ongoing clinical trials and further research may shed more light on the subject in the future.ConclusionBCG is a multifaceted vaccine, with many numerous potential applications to vaccination strategies being employed for current and future viral infections. There however is a need for further studies into the immunologic mechanisms behind these non-specific effects, for these potentials to become reality, as we usher in the beginning of the second century since the vaccine's discovery.