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academies
Ann Biol Sci, 2017
ISSN: 2348-1927
August 23-24, 2017 | Toronto, Canada
Annual Conference on
MICROBIAL PATHOGENESIS, INFECTIOUS DISEASE,
ANTIMICROBIALS AND DRUG RESISTANCE
Arch Clin Microbiol, 8:5
DOI: 10.4172/1989-8436-C1-003
H
uman genetic studies together with data from mouse
models indicate that variations in the expression
of Macrophage Migration Inhibitory Factor (MIF) affect
the severity of different infections. MIF is expressed by
the innate response to promote pathways necessary for
pathogen clearance. Functional polymorphisms in the MIF
gene (MIF) occur commonly, with the lowest expression
promoter variants present in 45-78% of studied populations.
In community-acquired pneumonia, high genotypic MIF
expressers show a 50% increased survival benefit when
compared to low genotypic MIF expressers. There is
population stratification at the MIF locus and evidence for
allelic selection in regions endemic for malaria, where low
genotypic MIF expression appears to protect from the lethal
inflammatory sequelae of infection. Evidence of MIF’s role
in protection from Mycobacterium infection has prompted
examination of the potential contribution of MIF alleles to
the high prevalence of TB in Africa. In an HIV+ cohort, genetic
low expressers of MIF were 2.4 times more frequently
identified among patients with Mycobacterium bacteremia
than those without. A higher prevalence of low expression
alleles among TB cases than controls without active TB
also was observed. As South Africans show the highest
global prevalence of low expression MIF alleles, this finding
suggests a contribution of functional MIF polymorphisms to
the high prevalence of TB in this population. Insights into the
structure-function relationship between MIF and its receptor
have enabled the design of first-in-class small molecule MIF
agonists that enhance MIF binding and signal transduction.
One MIF agonist (MIF20) shows beneficial action in mouse
models of Mycobacterium and S. pneumoniae infection.
Pharmacologic augmentation of MIF, which is in pre-clinical
development, may be a useful strategy in low genotypic MIF
expressers. Such an approach may be especially beneficial as
adjunctive therapy in resistant or difficult to treat infections
as in MDR and XDR TB.
e
:
Richard.Bucala@Yale.eduPrecision medicine for infectious diseases at the MIF locus
Richard Bucala
Yale Schools of Medicine and Public Health, USA