AUTHOR=Ritchie Jennifer , Rupper Adam , Cardelli James , Bellaire Bryan 

TITLE=Host interferon-γ inducible protein contributes to Brucella survival

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=2

YEAR=2012

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2012.00055

DOI=10.3389/fcimb.2012.00055

ISSN=2235-2988

ABSTRACT=<p><italic>Brucella</italic> spp. are highly adapted intracellular pathogens of mammals that cause chronic infections while surving and replicating in host monocytes and macrophages. Although monocytes are normally susceptible to infection, pretreatment with pro-inflammatory cytokine interferon-γ (IFN-γ) activates cellular defense mechanisms that increase intracellular killing of <italic>Brucella</italic> and prevents bacterial replication. We examined the contribution of the IFN-γ inducible GTPase, LRG-47, to <italic>B. abortus</italic> 2308 infection in <italic>in vitro</italic> and <italic>in vivo</italic> murine models. Infecting non-activated macrophages from LRG-47<sup>−/−</sup> mice revealed that loss of this host protein negatively effected the intracellular survival and replication of IgG opsonized <italic>B. abortus</italic>. In contrast, survival and replication of non-opsonized <italic>B. abortus</italic> was the same in both C57/B6 and LRG-47<sup>−/−</sup> peritoneal macrophages. Following IFN-γ activation of LRG-47<sup>−/−</sup> monocytes, IgG opsonized <italic>B. abortus</italic> survived better than non-opsonized bacteria. The differential fate of opsonized and non-opsonized <italic>B. abortus</italic> was only observed in macrophages collected from LRG-47<sup>−/−</sup> mice. Given the specific nature of the relationship between this host protein and the mechanism of <italic>Brucella</italic> internalization, LRG-47<sup>−/−</sup> mice were infected with <italic>B. abortus</italic> to assess whether the loss of the lrg47 protein would affect the ability of the bacteria to colonize or persist within the host. <italic>B. abortus</italic> were able to establish and maintain similar numbers of bacteria in both C57/B6 mice and LRG-47<sup>−/−</sup> through 3 weeks post intraperitoneal infection. By 9 weeks p.i. fewer <italic>B. abortus</italic> were recovered from LRG-47<sup>−/−</sup> mice than controls, suggesting that the host protein has a positive role in maintaining long term persistence of the bacteria within the host. These observations demonstrating a positive role for a host IFN-γ induced protein defense protein has yet to be reported. These results provide interesting insight into the complex interaction between <italic>Brucella</italic> and their host.</p>