title: Interleukin-17 mediated differences in the pathogenesis of HIV-1-associated tuberculous and cryptococcal meningitis.
abstract: OBJECTIVE
  Mycobacterium tuberculosis and Cryptococcus neoformans are major causes of meningitis in HIV-1-infected patients. Identifying differences in the inflammatory profiles of HIV-1-associated tuberculous meningitis (TBM) and cryptococcal meningitis may inform differences in immunopathogenic mechanisms in these diseases. In this study we compared the clinical and inflammatory features of HIV-1-associated TBM, and cryptococcal meningitis.
  
  
  METHODS
  A prospective study of HIV-1-infected adults who presented with either TBM [antiretroviral therapy (ART)-naive] or cryptococcal meningitis (regardless of ART prescription). Clinical and laboratory findings and concentrations of 40 inflammatory mediators measured in cerebrospinal fluid (CSF, 33 paired with blood) were compared between TBM and cryptococcal meningitis patients regardless of ART prescription and between TBM and cryptococcal meningitis patients not receiving ART.
  
  
  RESULTS
  Clinical and laboratory findings were similar in TBM (n=34) and cryptococcal meningitis (n = 19; ART prescribed: n = 10, no ART prescribed: n = 9). Exceptions included a higher median CD4 cell count [interquartile: 113 (69-199) vs. 25 (8-49) cells/μl, P = 0.0001] and higher HIV-1 median viral load [plasma: 5.46 (4.82-5.89) vs. 4.87 (4.36-5.17) log10copies/ml, P = 0.037; CSF: 6.05 (5.43-6.56) vs. 5.56 (4.52-5.80) log10copies/ml, P = 0.03] in TBM vs. cryptococcal meningitis patients not receiving ART. CSF interleukin (IL)-17A was lower in TBM compared with cryptococcal meningitis [1.00 (0.25-2.35) vs. 9.31 (1.24-23.36) pg/ml, P-adjusted = 0.03].
  
  
  CONCLUSIONS
  Despite presenting with higher peripheral CD4 cell counts, TBM patients also presented with higher HIV-1 viral loads compared with cryptococcal meningitis patients, suggesting a greater propensity of M. tuberculosis compared with C. neoformans to increase HIV-1 replication in vivo. CSF IL-17A was lower in TBM; its role in the immunopathogenesis of TBM and cryptococcal meningitis deserves further research.
authors.affiliation: aClinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular MedicinebDivision of Neurology, Department of Medicine, University of Cape TowncDepartment of Medicine, University of Cape Town, Cape Town, South AfricadDepartment of Medicine, Imperial CollegeeThe Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors.forename: Suzaan
authors.initials: S
authors.lastname: Marais
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.forename: Maia
authors.initials: M
authors.lastname: Lesosky
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D002555:Cerebrospinal Fluid / Q000737:chemistry; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D008297:Male; D016919:Meningitis, Cryptococcal / Q000453:epidemiology* / Q000473:pathology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D014390:Tuberculosis, Meningeal / Q000453:epidemiology* / Q000473:pathology*; D019562:Viral Load
chemical_list: D020381:Interleukin-17