Brucellosis is one of the most common global zoonoses and is caused by facultative intracellular bacteria of the genus
Brucella
. Numerous studies have found that MyD88 signaling contributes to protection against
Brucella
, however the underlying mechanism has not been entirely defined. Here we show that MyD88 signaling in hematopoietic cells contributes both to inflammation and to control of
Brucella melitensis
infection
in vivo
. While the protective role of MyD88 in
Brucella
infection has often been attributed to promotion of IFN-γ production, we found that MyD88 signaling restricts host colonization by
B. melitensis
even in the absence of IFN-γ.
In vitro
, we show that MyD88 promotes macrophage glycolysis in response to
B. melitensis
. Interestingly, a
B. melitensis
mutant lacking the glucose transporter, GluP, was more highly attenuated in MyD88
-/-
than in WT mice, suggesting MyD88 deficiency results in an increased availability of glucose
in vivo
which
Brucella
can exploit via GluP. Metabolite profiling of macrophages identified several metabolites regulated by MyD88 in response to
B. melitensis
, including itaconate. Subsequently, we found that itaconate has antibacterial effects against
Brucella
and also regulates the production of pro-inflammatory cytokines in
B. melitensis
-infected macrophages. Mice lacking the ability to produce itaconate were also more susceptible to
B. melitensis
in vivo
. Collectively, our findings indicate that MyD88-dependent changes in host metabolism contribute to control of
Brucella
infection.