cruzi metacyclic trypomastigotes, released in the faeces and urine of reduviid bugs taking a blood meal, invade keratinocytes and other cell types in the skin and mucosa [1–3]. Inside the host cells, trypomastigotes differentiate into amastigotes and undergo several cycles of replication by binary fission before redifferentiation into the non-dividing trypomastigotes. Upon exiting infected cells, trypomastigotes migrate through the extracellular matrix

to invade neighbouring cells or, through the circulation, distant cells in the heart, gastrointestinal tract, central nervous system and other organs. Repeated cellular cycles of T. cruzi Trametinib manufacturer invasion through the body are a characteristic feature of acute Chagas’ disease, which lasts only a few months. Acute disease ends when parasitemia becomes undetectable by optical microscopy, setting the stage for the onset of the

chronic phase of infection. This can be sub-divided in two clinical forms: 1) indeterminate, when patients are asymptomatic and selleck chemicals exhibit normal heart and digestive tract functions evaluated by electrocardiogram and radiography. And 2) symptomatic, when patients, for reasons that remain unknown, present pathological alterations that lead to electrical disturbances and enlargement of the heart (cardiomegaly), oesophagus (megaoesophagus) and/or colon (megacolon), accompanied by strong inflammation, fibrosis and destruction of the peripheral nervous system [4, 5]. Chronic Chagas’ infection, including those individuals in the indeterminate form, may last many years or decades. Innate and adaptive immunity play a critical role

in reducing parasite growth in the acute/chronic phase transition of Chagas’ disease and in maintaining low parasite burden that characterizes chronically infected individuals [6]. However, the relevant antigens, specific antigenic determinants and corresponding immune response governing these mechanisms remain incompletely understood. Recently, we discovered that sera of ∼80% patients with chronic Chagas’ disease contain Benzatropine autoantibodies (ATA) to TrkA, TrkB and TrkC, the tyrosine kinase receptors of the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), respectively [7], that underlie development and repair of the nervous system [8, 9]. As T. cruzi uses TrkA and TrkC to enter and activate neurons and glial cells [10–12], binding of ATA to TrkA and TrkC blocks invasion of neuronal, glial and non-neural cells in culture by the parasite [13]. Furthermore, when passively administered to mice, ATA potently blocked parasitemia, pathology and mortality [13]. Thus, ATA may represent a mechanism responsible for the low tissue parasitism that distinguishes chronic Chagas’ disease. If ATA reduces cellular invasion, underlying low tissue parasitism, then Trk autoimmunity should emerge in the acute phase of Chagas’ disease, as it ends with a drastic decline in parasitemia and tissue parasite load.