(Eh) y metanólico (Em) de Pera distichophylla sobre un aislado de ...
(Eh) y metanólico (Em) de Pera distichophylla sobre un aislado de ...
(Eh) y metanólico (Em) de Pera distichophylla sobre un aislado de ...
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M. T. GALáN-PUCHADES and A. OSUNA<br />
in an increase of T. cruzi parasitaemia, precisely<br />
one of the risks favouring vertical transmission.<br />
Additionally, helminths can also contribute to a<br />
lower IFN-g production via a predominant Th-2<br />
response in pregnant women. Therefore, it would<br />
be interesting to evaluate the helminthological<br />
status of chagasic pregnant women and its possible<br />
influence on vertical transmission.<br />
10<br />
DISCUSSION<br />
In or<strong>de</strong>r to address the questions of whether<br />
helminth infection could affect the susceptibility to<br />
subsequent co-infection with T. cruzi, and whether<br />
a changing environment and cytokine profile<br />
induced by worms may influence the outcome of<br />
CD compared with hosts exclusively infected with<br />
T. cruzi, it was fo<strong>un</strong>d that the presence of helminths<br />
modifies both the susceptibility and, in most cases,<br />
the course of CD.<br />
Concerning susceptibility, in all the studied hosts<br />
(humans, mice, dogs and primates) the presence<br />
of worms increases the likelihood to acquire CD<br />
mainly in the helminth chronic phase. In addition,<br />
co-infection seems to lengthen survivorship of coinfected<br />
hosts compared with those only harboring<br />
T. cruzi. The presence of helminths also tends to<br />
increase T. cruzi parasitaemia and certain helminths<br />
may even improve the health status of chagasic<br />
hosts.<br />
One of the main implications of these findings<br />
is that helminth co-infections could potentially<br />
modify the course of CD among patients with the<br />
same T. cruzi DTU (discrete typing <strong>un</strong>its) (Monteiro<br />
et al., 2007).<br />
In the last two <strong>de</strong>ca<strong>de</strong>s, studies explaining<br />
severe forms of CD have mainly been based on<br />
imm<strong>un</strong>ological findings (Dutra et al., 2005, Rodrigues<br />
et al., 2010). Chagasic myocarditis is<br />
thought to be due to the presence of parasites in<br />
the lesions. However, an <strong>un</strong>balanced imm<strong>un</strong>e homeostasis<br />
can trigger parallel autoimm<strong>un</strong>e phenomena<br />
which increase the imm<strong>un</strong>e response,<br />
thus worsening the outcome of the disease (Gutierrez<br />
et al., 2009). Several results evi<strong>de</strong>nce that an<br />
exacerbated Th1-like specific imm<strong>un</strong>e response<br />
against T. cruzi with high levels of IFN-γ and low<br />
levels of the anti-inflamatory cytokine IL-10 is established<br />
in T. cruzi-infected individuals present-<br />
ing cardiac disease (Gomes et al., 2003). In addition,<br />
there is some limited evi<strong>de</strong>nce regarding the<br />
role of Th17-mediated responses to T. cruzi. The<br />
IL-17 produced during the acute phase of CD controls<br />
cardiac inflammation by modulating the Th1<br />
response, and this pro-inflammatory IL-17 is also<br />
required for the elimination of T. cruzi (Gue<strong>de</strong>s et<br />
al., 2010; Miyazaki et al., 2010). In contrast IL-<br />
27, which suppresses Th17 responses, is beneficial<br />
for the host during T. cruzi infection (Yoshida<br />
and Miyazaki, 2008).<br />
Surprisingly, there is no mention in the literature<br />
that evaluates the possible role of helminth<br />
infections in human CD when helminths are able<br />
to suppress all types (Th1, Th2, and Th17) of responses<br />
(see ref Osada and Kanazawa, 2010).<br />
Consi<strong>de</strong>ring the classical Th1/Th2 paradigm, it is<br />
reasonable to speculate that a helminth-induced<br />
Th2 response with production of IL-4, IL-5, IL-6<br />
and IL-10 skewing with downregulation of Th1<br />
imm<strong>un</strong>e responses could result in an amelioration<br />
of Th1 diseases, such as CD. As IL-4 is known to<br />
suppress Th17 <strong>de</strong>velopment (Romagnani, 2006), a<br />
Th17 response could also be suppressed as well as<br />
Th1 response in helminth-infected hosts. In fact,<br />
certain helminth infections reduce IL-17 mRNA<br />
by MLN cells and inhibit IL-17 production (Elliot<br />
et al., 2008). This is of relevance when consi<strong>de</strong>ring<br />
persistent parasites such as helminths which<br />
are wi<strong>de</strong>ly distributed in humans in <strong>de</strong>veloping<br />
co<strong>un</strong>tries (Maizels et al., 1993), where they coexist<br />
with T. cruzi. Wormy populations are exposed to<br />
two potential risks, namely an increased susceptibility<br />
to T. cruzi and a yet <strong>un</strong>researched course of<br />
the disease. All of this should prompt research on<br />
the possible epi<strong>de</strong>miological relevance of helminth<br />
infections and the impact when controlling them<br />
on the inci<strong>de</strong>nce or the pathogenesis of CD. The<br />
presence of helminth co-infections may represent<br />
a much more important challenge for public health<br />
than recognized <strong>un</strong>til now.<br />
In other co-infections of human parasites such<br />
as malaria and hookworms, it has been stated<br />
that it would be possible to <strong>de</strong>fine co-infection<br />
as a specific “disease”, separate from malaria by<br />
itself, or hookworm by itself (Payne et al., 2009),<br />
and this may also hold true for CD and helminths.<br />
Thus, gathering more reliable data on the true<br />
parasitological status of all chagasic patients would<br />
be <strong>de</strong>sirable.<br />
Rev. Ibero-Latinoam. Parasitol. (2012); 71 (1): 5-13