Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy.

Highlights

  • Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a leading infectious cause of mortality worldwide

  • This study identified changes in the distribution of several immune cell subpopulations, expression of chemokine receptors, chemokine plasma levels, and migration capacity in multidrug-resistant TB (MDR-TB) and drugsensitive TB (DS-TB) patients

  • The expression of CD16 characterizes a proinflammatory monocyte subset that secretes a high amount of proinflammatory cytokines

Read more

Summary

Introduction

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a leading infectious cause of mortality worldwide. After reaching the lower respiratory tract, Mtb gets into contact with phagocytes, which respond by producing cytokines and chemokines These molecules mediate the recruitment of other leukocyte subsets, promoting the formation of multicellular immune structures termed granulomas [2]. We hypothesized that MDR-TB patients display phenotypical changes in chemokine receptors’ leukocyte expression compared to DS-TB individuals Their immune cell migration dynamics must be different and normalized after anti-MDR-TB therapy. We prospectively evaluated the frequency and distribution of several immune cell subpopulations expressing different chemokine receptors in the peripheral blood of DS-TB and MDR-TB patients. We analyze their migration capacity before and after anti-TB treatment. Our study contributes to a better understanding of the pathobiology of MDR-TB and uncovers immunological readouts that could serve as biomarkers for treatment monitoring

Materials and Methods
Results
Discussion
Conflicts of Interest
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call