B cell compartmentalization in blood and cerebrospinal fluid of HIV-infected ugandans with cryptococcal meningitis

Samuel Okurut, David B. Meya, Freddie Bwanga, Joseph Olobo, Michael A. Eller, Fatim Cham-Jallow, Paul R. Bohjanen, Harsh Pratap, Brent E. Palmer, Katharine H. Hullsiek, Yukari C. Manabe, David R. Boulware, Edward N. Janoff

Research output: Contribution to journalArticle

Abstract

Activated B cells modulate infection by differentiating into pathogenspecific antibody-producing effector plasmablasts/plasma cells, memory cells, and immune regulatory B cells. In this context, the B cell phenotypes that infiltrate the central nervous system during human immunodeficiency virus (HIV) and cryptococcal meningitis coinfection are ill defined. We characterized clinical parameters, mortality, and B cell phenotypes in blood and cerebrospinal fluid (CSF) by flow cytometry in HIV-infected adults with cryptococcal (n=31) and noncryptococcal (n=12) meningitis and in heathy control subjects with neither infection (n=10). Activation of circulating B cells (CD21low) was significantly higher in the blood of subjects with HIV infection than in that of healthy controls and greater yet in matched CSF B cells (P<0.001). Among B cell subsets, elevated frequencies of memory and plasmablasts/plasma cells most clearly distinguished the CSF from blood compartments. With cryptococcal meningitis, lower frequencies of expression of the regulatory protein programmed death-1 (PD-1) on plasmablasts/plasma cells in blood (median, 7%) at presentation were associated with significantly decreased 28-day survival (29% [4/14 subjects]), whereas higher PD-1 expression (median, 46%) characterized subjects with higher survival (88% [14/16 subjects]). With HIV infection, B cell differentiation and regulatory markers are discrete elements of the circulating and CSF compartments with clinical implications for cryptococcal disease outcome, potentially due to their effects on the fungus and other local immune cells.

Original languageEnglish (US)
Article numbere00779-19
JournalInfection and immunity
Volume88
Issue number3
DOIs
StatePublished - Mar 1 2020

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Keywords

  • Activation
  • B cell activation
  • B cell subsets
  • Blood
  • Cerebrospinal fluid
  • Cryptococcal meningitis
  • HIV
  • HIV coinfection
  • PD-1
  • PD-1 expression
  • Plasmablasts/plasma cells
  • Survival

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Okurut, S., Meya, D. B., Bwanga, F., Olobo, J., Eller, M. A., Cham-Jallow, F., Bohjanen, P. R., Pratap, H., Palmer, B. E., Hullsiek, K. H., Manabe, Y. C., Boulware, D. R., & Janoff, E. N. (2020). B cell compartmentalization in blood and cerebrospinal fluid of HIV-infected ugandans with cryptococcal meningitis. Infection and immunity, 88(3), [e00779-19]. https://doi.org/10.1128/IAI.00779-19