Reciprocal influences between leptin and glucocorticoids during acute Trypanosoma cruzi infection

ROMINA MANARIN, SILVINA RAQUEL VILLAR, RODRIGO FERNANDEZ BUSSY, FLORENCIA BELÉN GONZALEZ, EVA VERÓNICA DESCHUTTER, ANA PAULA BONANTINI, EDUARDO ROGGERO, ANA ROSA PÉREZ, OSCAR ADELMO BOTTASSO.

MEDICAL MICROBIOLOGY AND IMMUNOLOGY

SPRINGER

Lugar: Berlin; Año: 2013 p. 1 - 15

0300-8584

We recently showed that C57BL/6 mice undergoing an acute T. cruzi infectionrevealed a fatal disease associated to a dysregulated immune-endocrine response,characterized by a deleterious synthesis of TNF-a and glucocorticoid-driven thymusatrophy. Because metabolic response is also meaningful in the regulation of the overallhost response against infections, we decided to ascertain whether metabolic responseand the leptin/ObR circuitry may be playing a role in the susceptibility to T. cruziinfection. Infected mice displayed a series of metabolic abnormalities, i.e., reducedbody weight and food intake reduction, together with a manifest lipolysis andhypoglycemia. Infected mice had an increased TNF-a expression in adipose tissue andprofound alterations in the leptin/ObR circuitry, given the marked hypoleptinemia andabnormal ObR expression in the hypothalamus. Leptin administration to infectedanimals aggravated inflammation, lowered parasite burden and increased thymicatrophy with loss of natural regulatory T cells, while failing to normalize glycemia andcholesterolemia. Further studies in adrenalectomized mice showed that leptin levelswere even more diminished in infected mice, indicating that glucocorticoids arenecessary not only to decrease inflammation but also to sustain leptin secretion.Collectively, the immune-endocrine and metabolic changes seen during anuncontrolled T. cruzi infection also encompasses profound alterations in the adiposetissue and the leptin/ObR circuitry. Given the energetic cost of the anti-infectiousimmune response, such ineffective and dysregulated response may be also involved in the wasting state worsening the disease outcome.