Home Economics American Trypanosomiasis Chagas Disease, Second Edition: One Hundred Years of Research
Neutrophils are rapidly recruited at the site of infection39 and infiltrate infected organs. They contribute to eliminate parasites by uptaking and killing trypomastigotes (overall if they are opsonizd by Abs)40 as well as amastigotes released from infected tissues.41 A nice study showed recently that neutrophils generate extracellular traps (NETs) in the presence of T. cruzi in a TLR2 and TLR4-dependent manner,42 that help limit the infection by affecting the infectivity/pathogenicity of parasites.42 Neutrophils also produce cytokines/chemokines involved in shaping the immune response.43
Macrophages have received much attention as crucial players in host defense against T. cruzi as they simultaneously act as host cells and antigen-presenting cells.
Macrophage activation is a complex process involving coordinate/synergistic action of signals from cytokines, chemokines, and PAMPs.44 IFN-y is the most potent macrophage-activating factor, inducing “inflammatory” macrophages, called “M1.”45 Full macrophage activation requires previous priming that may be provided by low levels of IFNs. Some tissular macrophages are likely physiologically primed under homeostatic conditions.44 To avoid toxicity associated with excessive activation, IFNs concurrently induce the expression of the inhibitory proteins SOCS whereas TLR engagement induces the production of the macrophage deactivator IL-10.46
Priming of macrophages in T. cruzi infection may relate to type 1 IFNs produced at the site of parasite entry47 and IFN-y produced by iNKT cells. NK cell-derived IFN-y would play a role in a second step.39 Macrophage activation is strengthened later on when higher amounts of IFN-y are produced by T lymphocytes.48
T. cruzi activates mouse macrophages to produce IL-1, IL-12, TNF-a, IL-10, nitric oxide (NO), and ROS,49-51 and likely also IL-18 and IL-27.52,53 tGPI, Tc52, Ssp4, AgC10, and galactose moeities are all T. cruzi molecules able to directly activate macrophages.17,54-56 Inflammasomes play also a significant role in the IL-1(3
response.51,57 The parasite also activates human monocytes.58,59
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