Immunity & infection
Tuberculosis is an infectious disease that affects mainly thelungs, and represents a major health problem worldwide.
In recent years, the relationship between bioenergeticspathways and immune cell function has regained interest. Ithas been observed that glucolysis is enhaced duringtuberculosis, nevertheless glucolysis alone is not sufficient to sustain metabolic demands, and other metabolic pathwayshave barely been studied during this infection.
We analysed the expression of key enzymes of glutamionlysis; glutaminase (GLS) and glutamatedehydrogenase (GLUD); as well as succinate receptor(GPR91) and succinilated proteins (lysine hydroxilase and carboxymethyl lysine) in experimental pulmonarytuberculosis and human postmortem lung samples.
In experimental tuberculosis, glutaminase (GLS) expressionincreases during both early and progressive infection, meanwhile glutamate dehydrogenase (GLUD) only increasesduring early infection, suggesting that glutamine is fullyoxidized during early infection and partially oxidized duringprogressive infection. On the other side, succinate receptor GPR91 was overexpressed during early infection, and decreased on day 21 postinfection, suggesting that succinatemay act as a proinflammatory signal during early infection. It was also measured the expression of HIF1- α, whichincreased gradually during early infection until progressiveinfection.
In human postmortem lung samples there is enhacedexpression of GLS, GS, HIF-a, GPR91, lysine hydroxilaseand carboxymethyl lysine in tuberculosis positive patientscompared to controls.
The results from the experimental model suggests thatduring M. tuberculosis infection glutaminolysis increasesduring early infection and is associated with enhacedsuccinate signalling, probably through anapleroticproduction of succinate, that may be partially explained byHIF-1α expression. Succinate may act as pro-inflammatorystimuli, that decreases during progressive infection whenanti-inflammatory microenviroment prevale, althoughtpartial glutamine oxidation is still present. These findingsresemble to those in human samples.
Hospital General de Mexico Dr. Eduardo Liceaga
Instituto nacional de ciencias médicas y nutrición Salvador Zubiran