title: TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads.
abstract: BACKGROUND
  LILRA3 is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells. LILRA3 has a deletion genotype which is associated with multiple immune disorders. In this study, we wanted to analyze the regulation of LILRA3 and its significance in the context of HIV infection.
  
  
  RESULTS
  We analyzed a panel of TLR agonists and found that ssRNA40, a TLR8 agonist, is a potent inducer of LILRA3 in healthy individuals. However, this regulation is much diminished in HIV. Comparison of TLR8 to TLR4 induction of LILRA3 indicated that LPS induces less LILRA3 than ssRNA40 among healthy controls, but not HIV patients. Levels of LILRA3 induction correlated to virus load and CD4 counts in untreated patients. Recombinant LILRA3 can induce a host of proinflammatory genes which include IL-6 and IL-1α, as well as alter the expression of MHC and costimulatory molecules in monocytes and B-cells.
  
  
  CONCLUSIONS
  Our experiments point towards a beneficial role for LILRA3 in virus infections, especially in ssRNA viruses, like HIV, that engage TLR8. However, the potentially beneficial role of LILRA3 is abrogated during a HIV infection. We believe that more work has to be done to study the role of LILRA3 in infectious diseases and that there is a potential for exploring the use of LILRA3 in the treatment of virus infections.
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. low.huizhi@mh-hannover.de.
authors.forename: Hui Zhi
authors.identifier: http://orcid.org/0000-0002-3657-9371
authors.initials: HZ
authors.lastname: Low
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Ahrenstorf
authors.affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pommerenke
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Habermann
authors.affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany.|University of Veterinary Medicine, Hannover, Germany.|University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schughart
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Ordóñez
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Renata
authors.initials: R
authors.lastname: Stripecke
authors.affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Wilk
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D005786:Gene Expression Regulation; D006678:HIV / Q000302:isolation & purification*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000378:metabolism; D019562:Viral Load
chemical_list: C530062:LILRA3 protein, human; D011971:Receptors, Immunologic; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8
keywords: HIV; LILRA3; Monocytes; TLR4; TLR8