1921
Volume 100, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

B-cells have a spectrum of functions ranging from antibody production to antigen presentation and have additional vital roles in immune mechanisms. There is rudimentary knowledge about the role of B-cells in intracellular infections with contradictory findings. We explored the role of B-cell dysfunctions in visceral leishmaniasis (VL) pathogenesis in terms of the phenotypic and functional properties of B-cells during the course of disease. This study was performed on blood and splenic aspirates (SA) of VL cases pre- and post-treatment. Whole blood was used for flow cytometric studies for determining the profiles of B-cells at different time-points of treatment. Peripheral blood mononuclear cells were used for magnetic purification of B-cells, for transcriptional studies by real-time polymerase chain reaction (RT-PCR). Serum/plasma was used for direct agglutination test for determining parasite-specific antibodies and SA were used for scoring the presence of parasite by microscopic examination. Flow cytometric studies depicted decreased B-cell percentages during the entire course of disease and attainment of exhaustive phenotype with tissue-like memory cell markers, indicative of B-cell dysfunctions in VL. In addition, B-cells had compromised abilities of antigen processing and presentation and altered levels of B-lymphocyte–induced maturation protein-1 (Blimp-1). Blimp-1 expression goes hand in hand with B-cell maturation antigen and transmembrane activator and calcium modulator (TACI) and cyclophilin ligand interactor, suggestive of its role in promoting plasma cell survival and antibody production. Elevated level of VL-specific antibody titre was directly correlated with exhausted phenotype and also with disease severity during VL. This study indicated for impaired B-cell functions during chronic infection which may lead to pathological consequences in human VL.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.18-0350
2019-02-18
2020-09-25
Loading full text...

Full text loading...

/deliver/fulltext/14761645/100/4/tpmd180350.html?itemId=/content/journals/10.4269/ajtmh.18-0350&mimeType=html&fmt=ahah

References

  1. Ghose AC, Haldar JP, Pal SC, Mishra BP, Mishra KK, 1980. Serological investigations on Indian kala-azar. Clin Exp Immunol 40: 318326.
    [Google Scholar]
  2. Ronet C, Voigt H, Himmelrich H, Doucey MA, Hauyon-La Torre Y, Revaz-Breton M, Tacchini-Cottier F, Bron C, Louis J, Launois P, 2008. Leishmania major-specific B cells are necessary for Th2 cell development and susceptibility to L. major LV39 in BALB/c mice. J Immunol 180: 48254835.
    [Google Scholar]
  3. Miles SA, Conrad SM, Alves RG, Jeronimo SM, Mosser DM, 2005. A role for IgG immune complexes during infection with the intracellular pathogen Leishmania. J Exp Med 201: 747754.
    [Google Scholar]
  4. Woelbing F et al., 2006. Uptake of Leishmania major by dendritic cells is mediated by Fcgamma receptors and facilitates acquisition of protective immunity. J Exp Med 203: 177188.
    [Google Scholar]
  5. Moir S, Fauci AS, 2008. Pathogenic mechanisms of B-lymphocyte dysfunction in HIV disease. J Allergy Clin Immunol 122: 1219; quiz 20-1.
    [Google Scholar]
  6. Rousset F, Garcia E, Defrance T, Peronne C, Vezzio N, Hsu DH, Kastelein R, Moore KW, Banchereau J, 1992. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci U S A 89: 18901893.
    [Google Scholar]
  7. Rickert RC, Jellusova J, Miletic AV, 2011. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev 244: 115133.
    [Google Scholar]
  8. el Harith A, Kolk AH, Leeuwenburg J, Muigai R, Huigen E, Jelsma T, Kager PA, 1988. Improvement of a direct agglutination-test for field studies of visceral leishmaniasis. J Clin Microbiol 26: 13211325.
    [Google Scholar]
  9. Jacquet D, Boelaert M, Seaman J, Rijal S, Sundar S, Menten J, Magnus E, 2006. Comparative evaluation of freeze-dried and liquid antigens in the direct agglutination test for serodiagnosis of visceral leishmaniasis (ITMA-DAT/VL). Trop Med Int Health 11: 17771784.
    [Google Scholar]
  10. Davies CR, Mazloumi Gavgani AS, 1999. Age, acquired immunity and the risk of visceral leishmaniasis: a prospective study in Iran. Parasitology 119: 247257.
    [Google Scholar]
  11. Saha S, Ramachandran R, Hutin YJ, Gupte MD, 2009. Visceral leishmaniasis is preventable in a highly endemic village in West Bengal, India. Trans R Soc Trop Med Hyg 103: 737742.
    [Google Scholar]
  12. Avery DT et al., 2010. B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans. J Exp Med 207: 155171.
    [Google Scholar]
  13. Moir S et al., 2008. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med 205: 17971805.
    [Google Scholar]
  14. Portugal S et al., 2015. Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function. Elife 4: e07218.
    [Google Scholar]
  15. Minnich M, Tagoh H, Bonelt P, Axelsson E, Fischer M, Cebolla B, Tarakhovsky A, Nutt SL, Jaritz M, Busslinger M, 2016. Multifunctional role of the transcription factor Blimp-1 in coordinating plasma cell differentiation. Nat Immunol 17: 331343.
    [Google Scholar]
  16. Piskurich JF, Lin KI, Lin Y, Wang Y, Ting JP, Calame K, 2000. BLIMP-I mediates extinction of major histocompatibility class II transactivator expression in plasma cells. Nat Immunol 1: 526532.
    [Google Scholar]
  17. Silacci P, Mottet A, Steimle V, Reith W, Mach B, 1994. Developmental extinction of major histocompatibility complex class II gene expression in plasmocytes is mediated by silencing of the transactivator gene CIITA. J Exp Med 180: 13291336.
    [Google Scholar]
  18. Ghalib HW, Piuvezam MR, Skeiky YA, Siddig M, Hashim FA, el-Hassan AM, Russo DM, Reed SG, 1993. Interleukin 10 production correlates with pathology in human Leishmania donovani infections. J Clin Invest 92: 324329.
    [Google Scholar]
  19. Bouaziz JD, Calbo S, Maho-Vaillant M, Saussine A, Bagot M, Bensussan A, Musette P, 2010. IL-10 produced by activated human B cells regulates CD4(+) T-cell activation in vitro. Eur J Immunol 40: 26862691.
    [Google Scholar]
  20. Deak E, Jayakumar A, Cho KW, Goldsmith-Pestana K, Dondji B, Lambris JD, McMahon-Pratt D, 2010. Murine visceral leishmaniasis: IgM and polyclonal B-cell activation lead to disease exacerbation. Eur J Immunol 40: 13551368.
    [Google Scholar]
  21. Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, Gress RE, Hakim FT, Kochenderfer JN, 2013. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res 19: 20482060.
    [Google Scholar]
  22. Moreno I, Molina R, Torano A, Laurin E, Garcia E, Dominguez M, 2007. Comparative real-time kinetic analysis of human complement killing of Leishmania infantum promastigotes derived from axenic culture or from Phlebotomus perniciosus. Microbes Infect 9: 15741580.
    [Google Scholar]
  23. Dominguez M, Moreno I, Lopez-Trascasa M, Torano A, 2002. Complement interaction with trypanosomatid promastigotes in normal human serum. J Exp Med 195: 451459.
    [Google Scholar]
  24. Hasker E et al., 2014. Strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in India and Nepal. PLoS Negl Trop Dis 8: e2657.
    [Google Scholar]
  25. Kima PE, Constant SL, Hannum L, Colmenares M, Lee KS, Haberman AM, Shlomchik MJ, McMahon-Pratt D, 2000. Internalization of Leishmania mexicana complex amastigotes via the Fc receptor is required to sustain infection in murine cutaneous leishmaniasis. J Exp Med 191: 10631068.
    [Google Scholar]
  26. Halstead SB, O’Rourke EJ, 1977. Antibody-enhanced dengue virus infection in primate leukocytes. Nature 265: 739741.
    [Google Scholar]
  27. Chu N, Thomas BN, Patel SR, Buxbaum LU, 2010. IgG1 is pathogenic in Leishmania mexicana infection. J Immunol 185: 69396946.
    [Google Scholar]
  28. Wanasen N, Xin L, Soong L, 2008. Pathogenic role of B cells and antibodies in murine Leishmania amazonensis infection. Int J Parasitol 38: 417429.
    [Google Scholar]
  29. Smelt SC, Cotterell SE, Engwerda CR, Kaye PM, 2000. B cell-deficient mice are highly resistant to Leishmania donovani infection, but develop neutrophil-mediated tissue pathology. J Immunol 164: 36813688.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.18-0350
Loading
/content/journals/10.4269/ajtmh.18-0350
Loading

Data & Media loading...

  • Received : 24 Apr 2018
  • Accepted : 14 Oct 2018
  • Published online : 18 Feb 2019
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error