ABSTRACT
T cell activation markers (TAM) expressed by antigen-specific T cells constitute promising candidates to attest the presence of an active infection by Mycobacterium tuberculosis (Mtb). Reciprocally, their modulation may be used to assess antibiotic treatment efficacy and eventually attest disease resolution. We hypothesized that the phenotype of Mtb-specific T cells may be quantitatively impacted by the load of bacteria present in a patient. We recruited 105 Tanzanian adult tuberculosis (TB) patients and obtained blood before and after 5 months of antibiotic treatment. We studied relationships between patients’ clinical characteristics of disease severity and microbiological as well as molecular proxies of bacterial load in sputum at the time of diagnosis. Besides, we measured by flow cytometry the expression of CD38 or CD27 on CD4+ T cells producing interferon gamma (IFN-γ) and/or tumor necrosis factor-alpha (TNF-α) in response to a synthetic peptide pool covering the sequences of Mtb antigens ESAT-6, CFP-10 and TB10.4. Reflecting the difficulty to extrapolate bacterial burden from a single end-point read-out, we observed statistically significant, but weak, correlations between Xpert MTB/RIF, MBLA and time to culture positivity. Unlike CD27, the resolution of CD38 expression by antigen-specific T cells was observed readily following 5 months of antibiotic therapy. In addition, only the intensity of CD38-TAM signals measured at diagnosis significantly correlated with Mtb 16S RNA recovered from patients’ sputa. Altogether, our data support CD38-TAM as an accurate marker of infection resolution and a sputum-independent proxy of bacterial load.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
Funds supporting this study were received from The Swiss National Science Foundation (Grant number 177163)
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The study protocol was approved by the institutional review board of the Ifakara Health Institute (IHI; reference no. IHI/IRB/EXT/No: 16-2019) and the Medical Research Coordinating Committee of the National Institute for Medical Research (NIMR; reference no.NIMR/HQ/R.8a/Vol.IX/1641) in Tanzania. All participants provided a signed informed consent to collect clinical data, sputum and blood samples. In case of illiteracy, study information was given in the presence of an impartial, literate witness, who read the information sheet to the participant or witnessed the complete reading of the information sheet to the participant.
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Data Availability
All data produced in the present study are available upon reasonable request to the authors