Circulating IgA/IgG memory B cells against Mycobacterium tuberculosis dormancy-associated antigens Rv2659c and Rv3128c in active and latent tuberculosis

Soe, Phyu Thwe; Hanthamrongwit, Jariya; Saelee, Chutiphon; Kyaw, Soe Paing; Khaenam, Prasong; Warit, Saradee; Satproedprai, Nusara; Mahasirimongkol, Surakameth; Yanai, Hideki; Chootong, Patchanee; Leepiyasakulchai, Chaniya

doi:10.1016/j.ijid.2021.07.033

Cited by 7 publications

(14 citation statements)

References 45 publications

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“…Another limitation of ELISPOT method is that the MBCs need to be pre-activated in vitro in order to convert to ASCs. In the flow cytometry-based studies, frequencies of cMBC were found significantly higher and those of PBs significantly lower in LTBI than in active TB [ 9 , 25 , 26 ]. In addition, Zimmermann et al [ 9 ] showed that antibodies produced by PBs preferentially targeted the MtM antigens.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, Zimmermann et al [ 9 ] showed that antibodies produced by PBs preferentially targeted the MtM antigens. In ELISPOT based studies also, the frequency of antigen-specific MBCs was higher and PBs was lower in LTBI than in active TB [ 24 , 25 , 27 ]. However, reports on class-switched cMBCs or aMBCs are scanty, even contradictory [ 25 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Distinct and shared B cell responses of tuberculosis patients and their household contacts

Singh

Kumar²,

Umam³

et al. 2022

PLoS ONE

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This study was aimed at identifying the B cell responses which could distinguish between ‘latent tuberculosis infection (LTBI)’ and active TB disease. Study subjects were smear-positive TB patients (n = 54) and their disease-free household contacts (HHCs, n = 120). The sera were used for determination of antibody levels (ΔOD values) against Mycobacterium tuberculosis membrane (MtM) antigens by ELISA and for visualisation of seroreactive MtM antigens by immunoblotting. B cell subsets in whole blood samples were determined by flow cytometry. In TB sera, levels of IgG antibodies were significantly higher than IgM and IgA whereas IgM and IgA antibody levels were comparable. Conversely, HHC sera had significantly higher IgM antibody levels than IgG and IgA. The ratio of IgM to IgG antibodies in HHCs were also significantly higher than in patients. Immunoblotting revealed that some of the MtM antigens (<10, ~12 and ~25 kDa) reacted with TB as well as HHC sera whereas some other antigens (~16, ~36, ~45 and ~60 kDa) reacted with most of TB and a subset of HHC sera. Frequencies of classical memory B cells (cMBCs, CD19+CD27+) were significantly higher, and of IgG+ cMBCs were significantly lower in HHCs than in patients. Frequencies of IgA+ cMBCs in HHCs and patients were comparable but both were significantly higher than the corresponding frequencies of IgG+ cMBCs. Frequencies of IgA+ atypical MBCs (aMBCs, CD19+CD27-) in HHCs and patients were also comparable and significantly higher than the IgG+ aMBCs. The plasmablast (CD19+CD27++CD38++) frequencies in HHCs and patients were comparable. These results suggest that the IgM/IgG antibody ratio, antibody binding to selected MtM antigens and relative frequencies of MBC subsets could indicate protective or pathogenic immune responses following the primary infection with Mtb. Responses that orchestrate protection leading to a ‘quiescent’ LTBI may provide clues to an effective vaccination strategy against TB.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distinct and shared B cell responses of tuberculosis patients and their household contacts

Singh

Kumar²,

Umam³

et al. 2022

PLoS ONE

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“…In this study, proteins Rv2659c and Rv1738 were proposed to elucidate their innate immune induction ability since a role in adaptive immunity was revealed previously [ 25 – 28 ]. We demonstrated that proteins Rv2659c and Rv1738 were recognized by hTLR2 and hTLR4 using HEK-Blue engineered cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant dormancy-associated Mycobacterium tuberculosis proteins Rv2659c and Rv1738 were expressed using the same protocol as described previously [25]. In brief, genomics of Rv2659c (1,128 bp) and Rv1738 (285 bp) using Mtb H37Rv strain were amplified and cloned in expression plasmids (pET24b for Rv2659c and pET28a for Rv1738), then introduced into Escherichia coli (E. coli) BL21 (DE3) with the induction of 0.5 mM IPTG at 37˚C for 3 hours.…”

Section: Molecular Cloning and Protein Expressionmentioning

confidence: 99%

“…Interestingly, the peptides of Rv2659c and Rv1738 were predominantly recognized by IgA in the sera of latent tuberculosis individuals (LTBIs) (unpublished data). Later we found that the number of specific recombinant protein Rv2659c IgA memory B cells (MBCs) presented in LTBIs is higher than in those with active tuberculosis [ 25 ]. Others showed that protein Rv2659c exerts its ability to escalate frequency of CD4 + T cells and co-expression of cytokines (IFN-γ, TNF-α and IL-2) in LTBI [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Toll-like receptor-mediated innate immune responses by recognition of the recombinant dormancy-associated Mycobacterium tuberculosis proteins Rv2659c and Rv1738

et al. 2022

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Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) poses a major threat to the global public health. Importantly, latent tuberculosis infection (LTBI) still impedes the elimination of TB incidence since it has a substantial risk to develop active disease. A multi-stage subunit vaccine comprising active and latency antigens of Mtb has been raised as the promising vaccine to trigger immune protection against all stages of TB. Therefore, the discovery of new antigens that could trigger broad immune response is essential. While current development of TB vaccine mainly focuses on protective immunity mediated by adaptive immune response, the knowledge on triggering the innate immune response by antigens is still limited. We showed that recombinant dormancy-associated Mtb proteins Rv2659c and Rv1738 were recognized by human innate immune recognition molecules, Toll-like receptors (TLRs) 2 and 4 by using HEK-Blue™ hTLR2/hTLR4 systems. We further demonstrated that these two proteins activated phosphorylated NF-κB p65 (Ser536) in the human CD14+ blood cells. We also investigated that these two proteins significantly induced level of pro- and anti-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10 and TNF-α) which were mediated through TLR2 and TLR4 pathways in human peripheral blood mononuclear cells (hPBMCs). These findings suggest that proteins Rv2659c and Rv1738 stimulated innate immune response targeting TLR2 and TLR4 to produce inflammatory cytokines, and their benefits would be valuable for the development of an effective prophylactic tuberculosis vaccine.

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Revisiting tuberculosis screening: An insight to complementary diagnosis and prospective molecular approaches for the recognition of the dormant TB infection in human and cattle hosts

Álvarez

2021

Microbiological Research

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Circulating IgA/IgG memory B cells against Mycobacterium tuberculosis dormancy-associated antigens Rv2659c and Rv3128c in active and latent tuberculosis

Cited by 7 publications

References 45 publications

Distinct and shared B cell responses of tuberculosis patients and their household contacts

Distinct and shared B cell responses of tuberculosis patients and their household contacts

Toll-like receptor-mediated innate immune responses by recognition of the recombinant dormancy-associated Mycobacterium tuberculosis proteins Rv2659c and Rv1738

Revisiting tuberculosis screening: An insight to complementary diagnosis and prospective molecular approaches for the recognition of the dormant TB infection in human and cattle hosts

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