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Microbiology: Current Research 2017
Volume 1 Issue 2 Microbes Infection 2017
Notes:
Page 39
September 28-29, 2017 | London, UK
Microbes Infection
38th Annual congress on
THE ANTI-HIV CANDIDATE ABX464
DAMPENS INTESTINAL INFLAMMATION
BY TRIGGERING IL22 PRODUCTION IN
ACTIVATED MACROPHAGES
Jamal Tazi1,2
1University of Montpellier, France
2ABIVAX-CNRS Cooperative Laboratory, Montpellier, France
The progression of human immunodeficiency virus (HIV)
is associated with mucosal damage in the gastrointestinal
(GI) tract. This damage enables bacterial translocation from
the gut and leads to subsequent inflammation. Dextran sulfate
sodium (DSS-treatment) is an established animal model for
experimental colitis that was recently shown to recapitulate
the link between GI-tract damage and pathogenic features
of SIV infection. The current study tested the protective
properties of ABX464, a first-in-class anti-HIV drug
candidate that has demonstrated anti-viral activity in HIV
treatment of naïve patients. ABX464 also induced a long-
lasting control of the viral load in HIV infected humanized
mice after treatment arrest. ABX464 treatment strongly
attenuated DSS-induced colitis in mice and produced a
long-term protection against prolonged DSS-exposure after
drug cessation. Consistently, ABX464 reduced the colonic
production of the inflammatory cytokines IL-6 and TNF as
well as that of the chemoattractant MCP-1. However, RNA
profiling analysis revealed the capacity of ABX464 to induce
the expression of IL-22, a cytokine involved in colitis tissue
repair both in DSS-treated mice. A comprehensive analysis
of the gene expression profiles by RNAseq demonstrated
that the expression of IL22 was preferentially induced by
ABX464 in mouse bone marrow derived macrophages only
upon stimulation with LPS. Importantly, anti-IL22 antibodies
abrogated the protective effect of ABX464 on colitis in DSS-
treated mice. Because reduced IL-22 production in the gut
mucosa is an established factor of HIV and DSS-induced
immunopathogenesis, our data suggest that the anti-
inflammatory properties of ABX464 warrant exploration in
both HIV and inflammatory ulcerative colitis (UC) disease.
In the DSS induced colitis model, ABX464 protects mice from
inflammatory response: Prevention of weight loss and colon
size; Reduced macrophage recruitment into the intestine;
Decreased levels of pro-inflammatory cytokines; Long-lasting
effect (like in the HIV humanized mouse model).
Microbiology: Current Research 2017