Effects of B cell depletion on early Mycobacterium tuberculosis infection in cynomolgus macaques

Jiayao Phuah, Eileen A. Wong, Hannah P. Gideon, Pauline Maiello, M. Teresa Coleman, Matthew R. Hendricks, Rachel Ruden, Lauren R. Cirrincione, John Chan, Philana Ling Lin, Jo Anne L Flynn

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Although recent studies in mice have shown that components of B cell and humoral immunity can modulate the immune responses against Mycobacterium tuberculosis, the roles of these components in human and nonhuman primate infections are unknown. The cynomolgus macaque (Macaca fascicularis) model of M. tuberculosis infection closely mirrors the infection outcomes and pathology in human tuberculosis (TB). The present study used rituximab, an anti-CD20 antibody, to deplete B cells in M. tuberculosis-infected macaques to examine the contribution of B cells and humoral immunity to the control of TB in nonhuman primates during the acute phase of infection. While there was no difference in the overall pathology, disease profession, and clinical outcome between the rituximab-treated and untreated macaques in acute infection, analyzing individual granulomas revealed that B cell depletion resulted in altered local T cell and cytokine responses, increased bacterial burden, and lower levels of inflammation. There were elevated frequencies of T cells producing interleukin-2 (IL-2), IL-10, and IL-17 and decreased IL-6 and IL-10 levels within granulomas from B cell-depleted animals. The effects of B cell depletion varied among granulomas in an individual animal, as well as among animals, underscoring the previously reported heterogeneity of local immunologic characteristics of tuberculous granulomas in nonhuman primates. Taken together, our data clearly showed that B cells can modulate the local granulomatous response in M. tuberculosis-infected macaques during acute infection. The impact of these alterations on disease progression and outcome in the chronic phase remains to be determined.

Original languageEnglish (US)
Pages (from-to)1301-1311
Number of pages11
JournalInfection and Immunity
Volume84
Issue number5
DOIs
StatePublished - May 1 2016

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Mycobacterium Infections
Macaca
Mycobacterium tuberculosis
B-Lymphocytes
Granuloma
Primates
Infection
Humoral Immunity
Interleukin-10
Tuberculosis
Pathology
T-Lymphocytes
Macaca fascicularis
Interleukin-17
Interleukin-2
Disease Progression
Anti-Idiotypic Antibodies
Interleukin-6
Cytokines
Inflammation

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Phuah, J., Wong, E. A., Gideon, H. P., Maiello, P., Coleman, M. T., Hendricks, M. R., ... Flynn, J. A. L. (2016). Effects of B cell depletion on early Mycobacterium tuberculosis infection in cynomolgus macaques. Infection and Immunity, 84(5), 1301-1311. https://doi.org/10.1128/IAI.00083-16

Effects of B cell depletion on early Mycobacterium tuberculosis infection in cynomolgus macaques. / Phuah, Jiayao; Wong, Eileen A.; Gideon, Hannah P.; Maiello, Pauline; Coleman, M. Teresa; Hendricks, Matthew R.; Ruden, Rachel; Cirrincione, Lauren R.; Chan, John; Lin, Philana Ling; Flynn, Jo Anne L.

In: Infection and Immunity, Vol. 84, No. 5, 01.05.2016, p. 1301-1311.

Research output: Contribution to journalArticle

Phuah, J, Wong, EA, Gideon, HP, Maiello, P, Coleman, MT, Hendricks, MR, Ruden, R, Cirrincione, LR, Chan, J, Lin, PL & Flynn, JAL 2016, 'Effects of B cell depletion on early Mycobacterium tuberculosis infection in cynomolgus macaques', Infection and Immunity, vol. 84, no. 5, pp. 1301-1311. https://doi.org/10.1128/IAI.00083-16
Phuah J, Wong EA, Gideon HP, Maiello P, Coleman MT, Hendricks MR et al. Effects of B cell depletion on early Mycobacterium tuberculosis infection in cynomolgus macaques. Infection and Immunity. 2016 May 1;84(5):1301-1311. https://doi.org/10.1128/IAI.00083-16
Phuah, Jiayao ; Wong, Eileen A. ; Gideon, Hannah P. ; Maiello, Pauline ; Coleman, M. Teresa ; Hendricks, Matthew R. ; Ruden, Rachel ; Cirrincione, Lauren R. ; Chan, John ; Lin, Philana Ling ; Flynn, Jo Anne L. / Effects of B cell depletion on early Mycobacterium tuberculosis infection in cynomolgus macaques. In: Infection and Immunity. 2016 ; Vol. 84, No. 5. pp. 1301-1311.
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