Modulation of Mycobacterium tuberculosis-specific humoral immune responses is associated with Strongyloides stercoralis co-infection

Ray, Anuradha; Munisankar, Saravanan; Bhootra, Yukti; Dolla, Chandrakumar; Kumaran, Paul; Nutman, Thomas B.; Babu, Subash

doi:10.1371/journal.pntd.0005569

Cited by 13 publications

(15 citation statements)

References 32 publications

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“…The elevation of BAFF was closely related to the Th1 immune response (17). When co-infected with Strongyloides stercoralis, BAFF and APRIL level significantly diminished in comparison to these patients with latent TB (23). In our study, we found that BAFF levels were dramatic increased in TPE patients, particularly in the pleural effusion of these patients.…”

Section: Discussionsupporting

confidence: 56%

Increased B�cell activating factor is associated with B�cell class switching in patients with tuberculous pleural effusion

et al. 2018

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B cell activating factor (BAFF), a member of the tumor necrosis factor family, is a key cytokine for B cell survival, a function that is essential for B cell maturation and memory. The expression levels of BAFF and its potential contribution to B cell maturation remain elusive in patients with tuberculous pleural effusion (TPE). The present study enrolled 40 healthy controls (HC) and 45 TPE patients, and investigated the levels of BAFF in the plasma and pleural effusion. Concomitantly, B cell subsets including naïve B cell (CD19+IgD+CD27‑), unswitched B cell (CD19+IgD+CD27+), switched B cell (CD19+IgD‑CD27+), total memory B cell (CD19+CD27+), plasma B cell (CD19+IgD‑CD38+CD27+) and transitional B cell (CD19+IgDdim CD38+) in peripheral blood mononuclear cells (PBMCs) and pleural fluid mononuclear cells (PFMCs) were assessed using multicolor flow cytometry. Finally, the associations between BAFF and each sub‑group of B cells in TPE patients were analyzed. Compared with HC cases, an increased BAFF level and elevated frequency of switched B cell were observed in the blood and pleural effusion from patients with TPE. The proportions of naïve B cell, plasma B cell and transitional B cell were lower in the PFMCs of TPE patients. Furthermore, a significant correlation was observed between the level of BAFF, and the proportion of switched B cell in the peripheral blood and pleural effusion of TPE patients. These findings indicated that the B cell profile may be different in the pleural effusion, and BAFF may activate switched B cells to enhance the humoral immune responses in patients with TPE. Further studies are required to elucidate the underlying mechanisms and determine the potential immunotherapy of the BAFF‑switched B cell axis.

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Section: Discussionsupporting

confidence: 56%

Increased B�cell activating factor is associated with B�cell class switching in patients with tuberculous pleural effusion

et al. 2018

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“…In another study, APRIL expression was shown to be increased in B cells of M. tuberculosis-infected patients after 6 months of anti-M. tuberculosis treatment (140). Finally, a recent study confirmed the BAFF-and APRIL-inducing effect of M. tuberculosis by measuring serum BAFF and APRIL levels in patients with latent M. tuberculosis infection (141). Although the levels of both cytokines were increased in these patients, a significant correlation was present only between BAFF and IgG levels.…”

Section: Bacteria Bacterial Infections Of the Respiratory Systemmentioning

confidence: 87%

“…The correlation between elevated BAFF levels during the acute phase of HCV infection and poor disease prognosis is a good example of this phenomenon. Furthermore, the breakage of tolerance as a consequence of chronic exposure to BAFF-inducing viruses (HIV and HCV) or parasites (T. cruzi) may be related to the preferential activation of polyreactive MZ B cells (14,141,142,168,169). Pathogens susceptible to antibody-mediated microbicidal host responses appear to prevent the development of antibody responses by downregulating the expression of BAFF and APRIL receptors.…”

Section: Discussionmentioning

confidence: 99%

The Role of BAFF System Molecules in Host Response to Pathogens

Sakai

Akkoyunlu

2017

Clin Microbiol Rev

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The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the "BAFF system molecules." BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development.

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“…Multiple studies performed in Mtb /helminth co-infected individuals have focused on the impact of helminth infection on 1) TB diagnosis [ 27 – 35 ], 2) reactivation of TB from latently infected individuals (LTBI) [ 36 , 37 ] and 3) BCG vaccine immunogenicity [ 38 – 40 ]. In addition, it was recently shown that helminth infection may interfere and/or influence innate [ 41 ], cellular [ 42 – 44 ] and humoral [ 45 ] immune responses to Mtb . However limited information is available on the cytokine profile of Mtb -specific T-cell immune responses in subjects with Mtb /helminth co-infection.…”

Section: Introductionmentioning

confidence: 99%

Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania

et al. 2017

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Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection.

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Modulation of Mycobacterium tuberculosis-specific humoral immune responses is associated with Strongyloides stercoralis co-infection

Cited by 13 publications

References 32 publications

Increased B�cell activating factor is associated with B�cell class switching in patients with tuberculous pleural effusion

Increased B�cell activating factor is associated with B�cell class switching in patients with tuberculous pleural effusion

The Role of BAFF System Molecules in Host Response to Pathogens

Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania

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