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. 2013;7(3):e2090.
doi: 10.1371/journal.pntd.0002090. Epub 2013 Mar 14.

Immunosuppression: cause for failures of vaccines against African Trypanosomiases

Henry Tabel  1 , Guojian Wei, Harold J Bull
Affiliations

Immunosuppression: cause for failures of vaccines against African Trypanosomiases

Henry Tabel et al. PLoS Negl Trop Dis. 2013.
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Mode of natural infections by African trypanosomes.
Infected tsetse flies bite the host by inserting the proboscis into the skin, inject saliva into the site, and puncture a small blood vessel, resulting in a small hemorrhage. The tsetse fly depicted here is sucking blood from the hemorrhage. During this process, trypanosomes are deposited into the skin. Trypanosomes enter the lymph system and then reach the draining lymph node and the bloodstream. Trypanosomes will circulate in the bloodstream. Whole trypanosomes or fractions thereof end up in macrophages of liver and spleen by antibody- and/or complement-mediated phagocytosis.
Figure 2
Figure 2. Minimal model: immunosuppression at primary intradermal infections by low numbers of trypanosomes.
Macrophages that have engulfed filopodia of trypanosomes or whole killed trypanosomes will process trypanosome antigens and present them at their cell surface. Glycosylphosphatidylinositol (GPI) of membrane variant surface glycoprotein (mVSG) will be presented via CD1d to NKT cells , . We argue that the NKT cells are predominantly type II NKT cells that release IL-13 which, in turn, skews the macrophages toward the M2 type. Thus, the antigen-presenting macrophages will predominantly be a mixed M1/M2 type (see text). MHC class II will present peptides to MHC class II–restricted T cells. The microenvironment will skew the naïve MHC class II–restricted T cells towards Tregs , , presumably via TGF-β produced by macrophages. Tregs, in turn, activate the Arg1 pathway of macrophages by production of IL-10. We propose that many of the naïve trypanosome-specific T cells that develop into Th1 effector cells are deleted by apoptosis, due to peroxynitrite (ONOO-) produced by macrophages under conditions of shortage of L-arginine supply , or are functionally impaired by down-regulation of CD3zeta .
See this image and copyright information in PMC

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