Sympathetic glial cells and macrophages develop different responses to Trypanosoma cruzi infection or lipopolysaccharide stimulation

Abstract

Nitric oxide (NO) participates in neuronal lesions in the digestive form of Chagas disease and the proximity of parasitised glial cells and neurons in damaged myenteric ganglia is a frequent finding. Glial cells have crucial roles in many neuropathological situations and are potential sources of NO. Here, we investigate peripheral glial cell response to Trypanosoma cruzi infection to clarify the role of these cells in the neuronal lesion pathogenesis of Chagas disease. We used primary glial cell cultures from superior cervical ganglion to investigate cell activation and NO production after T. cruzi infection or lipopolysaccharide (LPS) exposure in comparison to peritoneal macrophages. T. cruzi infection was greater in glial cells, despite similar levels of NO production in both cell types. Glial cells responded similarly to T. cruzi and LPS, but were less responsive to LPS than macrophages were. Our observations contribute to the understanding of Chagas disease pathogenesis, as based on the high susceptibility of autonomic glial cells to T. cruzi infection with subsequent NO production. Moreover, our findings will facilitate future research into the immune responses and activation mechanisms of peripheral glial cells, which are important for understanding the paradoxical responses of this cell type in neuronal lesions and neuroprotection.

Neuronal Parasitism, Early Myenteric Neurons Depopulation and Continuous Axonal Networking Damage as Underlying Mechanisms of the Experimental Intestinal Chagas' Disease

“…Loss of neuronal morphology or selective neuronal vulnerability to oxidative stress (Wang and Michaelis, 2010 ; Rivera et al, 2011 ) may be the reasons why previous in vivo and in vitro studies failed to detect neuronal invasion. The vulnerability of enteric neurons in CD was never studied before, and the resistance of superior cervical ganglion neurons to T. cruzi invasion (de Almeida-Leite et al, 2014 ) also needs further addressing. The in vivo approach adopted herein should allow a better evaluation of the role of neuronal invasion in neuronal death.…”

Metabolic syndrome agravates cardiovascular, oxidative and inflammatory dysfunction during the acute phase of Trypanosoma cruzi infection in mice

“…These cytokines stimulate macrophages to produce NO, the main effector required for the control of T . cruzi intracellular multiplication 64 , but its hyperproduction is also related to the severity of T . cruzi infection, mainly caused by tissue injury 8 .…”

Central nervous system commitment in Chagas disease

“…We should also point out that proinflammatory cytokines, as well as pathogen associated molecular patterns (LPS and poli:IC) induce depressive behavior ( 21 ). Accordingly, during CNS infection by T. cruzi , macrophages, microglia and astrocytes can release TNF-α, IL-1β, and nitric oxide -NO- ( 22 , 23 ), which seems to be related to neurological alterations observed in CD. Also, glutamate release is a common result of CNS infection, being induced by TNF-α and LPS ( 24 ).…”