Abstract
BackgroundLILRA3 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.ResultsWe 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.ConclusionOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0248-y) contains supplementary material, which is available to authorized users.
Highlights
leukocyte immunoglobulin like receptor A3 (LILRA3) is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells
Three of the four donors had a substantial upregulation of LILRA3 to TLR8 agonist ssRNA40 (Fig. 1a), but we did not observe any obvious pattern of upregulation in LILRB1 and LILRA1 expression (Additional file 1: Figure S1)
In order to confirm that TLR8 stimulation significantly upregulates LILRA3, we expanded the cohort using ssRNA40 stimulation, with ssRNA41 as a control
Summary
LILRA3 is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells. Extensive work has been done to functionally characterize members of the leukocyte immunoglobulin like receptor (LILR) family [1,2,3,4,5,6,7,8,9,10,11]. The function of leukocyte immunoglobulin like receptor A3 (LILRA3; ILT6; CD85e) has been less well characterized. The differentiation of monocytes into osteoclasts and dendritic cells has been shown to upregulate LILRA3 [12, 13]. It is the only member of the LILR family that. The homozygous deletion is found in 3 % of the healthy Caucasian population and confers susceptibility to some autoimmune diseases [17,18,19], HIV-infection (in revision), and B cell non-hodgkin lymphoma [20]
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