title: Virus infection stages and distinct Th1 or Th17/Th22 T-cell responses in malaria/SHIV coinfection correlate with different outcomes of disease.
abstract: BACKGROUND
  Malaria and AIDS represent 2 leading causes of death from infectious diseases worldwide, and their high geographic overlap means coinfection is prevalent. It remains unknown whether distinct immune responses during coinfection with malaria and human immunodeficiency virus (HIV) affect clinical outcomes.
  
  
  METHODS
  We tested this hypothesis by employing macaque models of coinfection with malaria and simian-human immunodeficiency virus (SHIV).
  
  
  RESULTS
  Plasmodium fragile malaria coinfection of acutely SHIV-infected macaques induced hyperimmune activation and remarkable expansion of CD4+ and CD8+ T effector cells de novo producing interferon γ or tumor necrosis factor α. Malaria-driven cellular hyperactivation/expansion and high-level Th1-cytokines enhanced SHIV disease characterized by increasing CD4+ T-cell depletion, profound lymphoid depletion or destruction, and even necrosis in lymph nodes and spleens. Importantly, malaria/SHIV-mediated depletion, destruction, and necrosis in lymphoid tissues led to bursting parasite replication and fatal virus-associated malaria. Surprisingly, chronically SHIV-infected macaques without AIDS employed different defense mechanisms during malaria coinfection, and mounted unique ∼200-fold expansion of interleukin 17+/interleukin 22+ T effectors with profound Th1 suppression. Such remarkable expansion of Th17/Th22 cells and inhibition of Th1 response coincided with development of immunity against fatal virus-associated malaria without accelerating SHIV disease.
  
  
  CONCLUSIONS
  These novel findings suggest that virus infection status and selected Th1 or Th17/Th22 responses after malaria/AIDS-virus coinfection correlate with distinct outcomes of virus infection and malaria.
authors.affiliation: Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago 60612, USA.
authors.forename: Bridgett
authors.initials: B
authors.lastname: Ryan-Payseur
authors.forename: Zahida
authors.initials: Z
authors.lastname: Ali
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Richard C
authors.initials: RC
authors.lastname: Wang
authors.forename: William E
authors.initials: WE
authors.lastname: Collins
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008253:Macaca mulatta; D008288:Malaria / Q000276:immunology*; D010961:Plasmodium / Q000276:immunology / Q000472:pathogenicity; D018419:Primate Diseases / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D016896:Treatment Outcome