Progression of visceral leishmaniasis due to Leishmania infantum in BALB/c mice is markedly slowed by prior infection with Trichinella spiralis

Abstract

We investigated in BALB/c mice the influence of the immunological environment created by the nematode Trichinella spiralis on the course of visceral leishmaniasis due to Leishmania infantum. On the day of Leishmania inoculation (day 0), mice, T. spiralis infected 7 days earlier, presented increased gamma interferon (IFN-␥), interleukin-4 (IL-4), and IL-5 mRNA levels locally and systemically and increased the potential of spleen cells to synthesize IFN-␥ and IL-4 after activation in vitro. Eighteen days after Leishmania inoculation (day 18), corresponding to the acute phase of leishmaniasis, the hepatic amastigote burden in mice coinfected with L. infantum and T. spiralis (LT mice) was significantly lower (P < 0.001) than that in mice infected with L. infantum only (L mice). IFN-␥ and IL-4 mRNAs were overexpressed in livers of LT and L mice. On day 70, corresponding to the chronic phase, the splenic amastigote load was significantly lower (P ‫؍‬ 0.004) in LT mice than it was in L mice. Splenic IFN-␥ transcripts were overexpressed in both L and LT mice. After Leishmaniaspecific in vitro stimulation, cytokine production was enhanced in both groups, but spleen cells from L mice produced significantly more IFN-␥ than did spleen cells from LT mice. Our data (i) generalize previous results indicating the lack of a clear-cut correlation between the outcome of murine visceral leishmaniasis and the type of cytokine pattern and (ii) demonstrate that in LT mice, leishmaniasis takes a markedly milder course than it does in L mice, providing information on the potential consequences of coinfection in a mammalian host.

Intestinal nematode infection exacerbates experimental visceral leishmaniasis

“…19 Despite what we know of the balance and antagonism between T-cell subsets, outcomes of coinfection models and clinical studies addressing this subject have not always been predictable. 20,21 In an experimental VL model where BALB/c mice were infected with Leishmania infantum seven days after Trichinella spiralis infection, coinfected mice had higher Leishmania burden, but surprisingly, IFNγ production was also elevated. 20 In contrast, preexisting, acute Strongyloides ratti infection was found not to affect L major lesions in C57BL/6 mice despite hampered IFNγ levels in draining lymph nodes.…”

“…20,21 In an experimental VL model where BALB/c mice were infected with Leishmania infantum seven days after Trichinella spiralis infection, coinfected mice had higher Leishmania burden, but surprisingly, IFNγ production was also elevated. 20 In contrast, preexisting, acute Strongyloides ratti infection was found not to affect L major lesions in C57BL/6 mice despite hampered IFNγ levels in draining lymph nodes. 21 burdens are high [24][25][26][27] and when the worm itself is in proximity to the secondary challenge.…”

Short- and Long-Term Efficacy of Hexadecylphosphocholine against EstablishedLeishmania infantumInfection in BALB/c Mice

“…We next demonstrated the short-term efficacy of HDPC against a Leishmania infection which evolved for 6 weeks prior to drug administration. This phase of murine leishmaniasis corresponds to the end of the acute phase of the disease (9) and is characterized by a spontaneous decrease of the hepatic and a steady increase of the splenic parasite burdens (9,32,38,51). In spite of the notable reduction of the amastigote load in the spleen, the splenomegaly was as important in HDPC-FIG.…”

“…L. infantum MON1 (MHOM/FR/94/LPN101), isolated from a patient with VL, was maintained by serial passages in Syrian hamsters. The promastigote form was cultured under usual conditions (38,42), and after three in vitro passages, stationary-phase cells from 7-day-old cultures were used at a concentration of 2.5 ϫ 10 7 promastigotes/ml to infect BALB/c mice. For infection the parasites were washed twice by sedimentation at 2,500 ϫ g at 4°C for 15 min each time, resuspended in 0.9% NaCl at 2 ϫ 10 8 cells/ml, and injected into caudal vein at 10 8 promastigotes/mouse.…”

“…In the next series of experiments we examined the capacity of HDPC to suppress L. infantum amastigotes in an established infection. Figure 1 shows a typical time course of VL in BALB/c mice (9,32,38,51). At 6 weeks after promastigote inoculation, i.e., at the end of the acute phase of the disease, the parasite load in the liver is decreasing but still high and in the spleen it is well detectable and increasing.…”