Metabolomics and lipidomics Palma et al.

A strong relationship between metabolic state and susceptibility
to Mycobacterium Tuberculosis (MTB)
infection exists. Indeed, intracellular energy metabolism sets the basis for an
exaggerated immuno-inflammatory response which concur to pathogenesis of MTB.
Herein, we show that controlled caloric restriction (CR), not leading to malnutrition,
induces control of MTB infection by dramatically reducing both bacterial load
and lung immunopathology in highly susceptible DBA/2 mice. CR reduced
significantly the production of pro-inflammatory cytokines in lung granulomas
as well as formation of foam cells, known to represent a major reservoir for
MTB replication. Mechanistically, CR induced a shift of the glucose metabolism
towards glycolysis in splenocytes and in T cells that associated with reduction
of the mechanistic target of rapamycin (mTOR) pathway in the lungs. Further, an
integrated multi-OMICS approach revealed a specific CR-induced metabolomic,
trascriptomic and proteomic signature leading to both reduced lung damage and slow
disease progression. Taken together our data suggest that CR represents a
feasible immunometabolic manipulation able to reverse a state of susceptibility
towards resistance to MTB infection, and that our approach offers a novel and
unexpected strategy to boost therapeutic interventions against MTB infection.