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. 2018 Apr 30;13(4):e0196470.
doi: 10.1371/journal.pone.0196470. eCollection 2018.

B cells response directed against Cut4 and CFP21 lipolytic enzymes in active and latent tuberculosis infections

Wendy Rénier  1 , Arnaud Bourdin  2 , Pierre-Alain Rubbo  1 , Marianne Peries  1 , Luc Dedieu  3 , Sophie Bendriss  1 , Laurent Kremer  4 , Stéphane Canaan  3 , Dominique Terru  1 , Sylvain Godreuil  1 , Nicolas Nagot  1 , Philippe Van de Perre  1 , Edouard Tuaillon  1
Affiliations

B cells response directed against Cut4 and CFP21 lipolytic enzymes in active and latent tuberculosis infections

Wendy Rénier et al. PLoS One. .

Abstract

Background: Better understanding of the immune response directed against Mycobacterium tuberculosis (Mtb) is critical for development of vaccine strategies and diagnosis tests. Previous studies suggested that Mtb enzymes involved in lipid metabolism, are associated with persistence and/or reactivation of dormant bacilli.

Methods: Circulating antibodies secreting cells (ASCs), memory B cells, and antibodies directed against Cut4 (Rv3452) and CFP21 (Rv1984c) antigens were explored in subjects with either active- or latent-tuberculosis (LTB), and in Mtb-uninfected individuals.

Results: Circulating anti-Cut4 ASCs were detected in 11/14 (78.6%) subjects from the active TB group vs. 4/17 (23.5%) from the LTB group (p = 0.001). Anti-CFP21 ASCs were found in 11/14 (78.6%) active TB vs. in 5/17 (29.4%) LTB cases (p = 0.01). Circulating anti-Cut4 and anti-CFP21 ASCs were not detected in 38 Mtb uninfected controls. Memory B cells directed against either Cut4 or CFP21 were identified in 8/11 (72.7%) and in 9/11 (81.8%) subjects with LTB infection, respectively, and in 2/6 Mtb uninfected individuals (33.3%). High level of anti-Cut4 and anti-CFP21 IgG were observed in active TB cases.

Conclusion: Circulating IgG SCs directed against Cut4 or CFP21 were mostly detected in patients presenting an active form of the disease, suggesting that TB reactivation triggers an immune response against these two antigens.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Anti-Cut4 and anti-CFP21 antibody circulating secreting cells (ASCs).
(A) Anti-Cut4 and anti-CFP21 ASCs from representative subjects of the three TB groups using ELISpot assay. 0.1 million enriched B cells were seeded per well. Quantification of cells secreting spontaneously anti-Cut4 IgG (B) and anti-CFP21 IgG (C) in Mtb uninfected subjects and subjects with LTB and active TB. The median values have been drawn as horizontal lines. Values of Wilcoxon Mann Withney tests are indicated.
Fig 2
Fig 2. Anti-Cut4 and anti-CFP21 memory B cells.
(A) Anti-Cut4 and anti-CFP21 ASCs after polyclonal stimulation from representative subjects of the Mtb uninfected and LTB groups, 1.105 enriched B cells were seeded per well. Quantification of ASC after five days of culture, anti-Cut4 IgG (B) and anti-CFP21 IgG (C) in Mtb uninfected and LTB subjects. The median values have been drawn as horizontal lines. Values of Wilcoxon Mann Withney tests are indicated.
Fig 3
Fig 3. Serum antibody (IgG) levels against CFP21, Cut4 and PPD.
The dot plots indicate level of antibodies directed against Cut4 (A), CFP21 (B), and PPD (C) in Mtb uninfected subjects, LTB subjects, and TB subjects. Antibodies levels are indicated per index of the optical density (OD), corresponding to the ratio of sample OD450nm/blank OD450nm.
See this image and copyright information in PMC

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