ABSTRACT
The proliferative response of CD4 and CD8 T lymphocytes obtained from C3H/HeN mice chronically infected with Trypanosoma cruzi strains that differ in virulence, tropism and immunogenicity, was assayed against skeletal muscle, sciatic nerve and spinal cord homogenates. Although both CD4 and CD8 T lymphocytes from mice infected with the RA strain strongly proliferated against the nervous system, no response against skeletal muscle antigens was detected. CD4 and CD8 T lymphocytes from mice infected with the K-98 clone (from CA-I strain) showed low proliferative response against all the antigens assayed. To determine whether the proliferation patterns showed correlation with T cell-mediated neuromuscular damage, passive cell transfer studies were performed. Fifteen days after transfer of CD4 T cells from RA-infected donors (CD4-RA), normal syngeneic recipients displayed exclusively nervous tissue damage, such as perineural, endoneural and/or meningeal inflammatory infiltrates, with predominance of CD4 T cells. Fifteen days after transfer of CD4 T lymphocytes from mice infected with K-98 (CD4-K98), recipients showed inflammatory infiltrates only in skeletal muscle, where CD4 T lymphocytes and macrophages were predominant cells. Recipients of CD8 T cells from RA-infected mice (CD8-RA) showed lesions in both spinal cord and sciatic nerves. Higher percentages of CD8 T cells were observed in comparison with the recipients of CD4-RA or CD4-K98. In contrast, CD8 T cells from K-98-infected donors (CD8-K98) did not induce tissue damage. These results provide evidence that mice infected with T. cruzi populations that differ in their biological characteristics show diverse immune mechanisms that may be involved in the pathogenesis of peripheral nervous system damage.
Subject(s)
Chagas Disease/complications , Chagas Disease/immunology , Neuromuscular Diseases/etiology , T-Lymphocyte Subsets/physiology , Adoptive Transfer , Animals , Antigens, Protozoan/immunology , CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/cytology , Cell Division , Chagas Disease/blood , Epitopes , Immunization, Passive , Male , Mice , Mice, Inbred C3H , Trypanosoma cruzi/immunologyABSTRACT
In this paper, we demonstrated that the production of PGE2 by CD8+ T lymphocytes through muscarinic cholinergic receptor (mAChR) activation of lymphocytes from mice acutely infected with nonlethal Trypanosoma cruzi CA-1 strain could enhance resistance to infection. Treatment in vivo with either atropine or cyclooxygenase inhibitors enhanced mortality rates and parasitemia of mice infected with T. cruzi CA-1 strain. The mechanism by which CD8+ T lymphocytes released PGE2 appears to involve the activation of the cells by circulating IgG present in mice infected with T. cruzi CA-1 strain. Binding of these antibodies to mAChR on CD8+ T lymphocytes triggered the release of large amounts of PGE2. The results point to a role of serum antibodies against mAChR in the protection of T. cruzi infection. The prostanoid acting as an immunomodulator contributed to the maintenance of the chronic course of experimental Chagas disease.
Subject(s)
Adjuvants, Immunologic/pharmacology , CD8-Positive T-Lymphocytes/chemistry , Chagas Disease/immunology , Dinoprostone/pharmacology , Receptors, Cholinergic/metabolism , Receptors, Muscarinic/metabolism , Animals , Atropine/pharmacology , Cell Membrane/parasitology , Chagas Disease/blood , Dinoprostone/blood , Immunity, Innate , Immunoglobulin G/metabolism , Male , Mice , Mice, Inbred BALB C , Muscarinic Antagonists/pharmacology , Receptors, Cholinergic/immunology , Receptors, Muscarinic/immunology , T-Lymphocytes/metabolism , Trypanosoma cruzi/isolation & purificationABSTRACT
PGE2 involvement in experimental Trypanosoma cruzi infection depends on the lethal capacity of the parasite subpopulation used. Mice acutely infected with non-lethal K98 displayed an enhancement in PGE2 serum levels during the acute period, while those infected with lethal T. cruzi subpopulations (RA or K98-2) showed levels not different from normal mice. The enhancement detected in K98 group could be related both to an increased number of CD8+ T cell number and to enhanced PGE2 release per cell by CD8+; values of PGE2 release by adherent cells were not altered in this group. Treatment with cyclooxygenase inhibitors enhanced mortality rates of mice infected with K98, and administration of 16,16-dimethyl PGE2 (dPGE) reversed this effect. However, mice infected with RA did not reduce their mortality rates by administration of diverse doses of dPGE. These findings suggest that PGE2 could play a role in resistance in mice infected with K98.
Subject(s)
Chagas Disease/metabolism , Dinoprostone/physiology , 16,16-Dimethylprostaglandin E2/pharmacology , Animals , Aspirin/pharmacology , Cell Adhesion , Chagas Disease/drug therapy , Chagas Disease/parasitology , Dinoprostone/biosynthesis , Dinoprostone/blood , Indomethacin/pharmacology , Leukocyte Count , Male , Mice , Mice, Inbred C3H , T-Lymphocytes/metabolism , Trypanosoma cruzi/pathogenicityABSTRACT
The macrophage function was investigated in mice infected with Trypanosoma cruzi. Two subpopulations of the parasite were utilized, RA and K98. Strain RA is efficiently internalized by macrophages and is lethal for mice, and clone K98 is poorly phagocytosed by macrophages and is not lethal. Treatment with silica enhanced parasitemia and mortality in mice infected with both parasite subpopulations. Parasitemia kinetics, however, were affected only in mice infected with RA, which suggests that macrophage effector mechanisms may play a more relevant role in this experimental group than in mice infected with K98. Resistance to Salmonella typhimurium infection and bactericidal activity of macrophages depended upon the T. cruzi subpopulation utilized and the infection period. Infection with K98 induced only a trend towards enhanced resistance to bacterial challenge during both the acute and chronic phases, whereas a significantly enhanced bactericidal activity of spleen and liver phagocytes was observed. Mice acutely infected with RA showed significantly enhanced susceptibility to S. typhimurium infection and lower bactericidal activity. Mice surviving infection with this aggressive strain, however, showed significantly enhanced resistance and bactericidal activities. Mice acutely infected with the RA strain displayed a dissociation between macrophage capacities to control S. typhimurium and T. cruzi. A similar phenomenon was also observed in other parasitoses (schistosomiasis, African trypanosomiasis). This fact may be due to differences in the lethal mechanisms through which macrophages control these parasites and S. typhimurium.
Subject(s)
Chagas Disease/immunology , Macrophages/immunology , Trypanosoma cruzi/pathogenicity , Acute Disease , Animals , Chagas Disease/parasitology , Chronic Disease , Immunity, Innate , Liver/microbiology , Macrophage Activation , Macrophages/parasitology , Macrophages/physiology , Male , Mice , Mice, Inbred C3H , Mononuclear Phagocyte System/immunology , Salmonella Infections, Animal/immunology , Salmonella typhimurium , Silicon Dioxide/pharmacology , Spleen/microbiology , VirulenceABSTRACT
Macrophage activation and production of opsonizing antibodies were studied in mice either infected with a lethal and reticulotropic Trypanosoma cruzi strain, RA, or with a non lethal and myotropic strain, CA-I, as well as with a clone, K98 (derived from CA-I), similar to the parental strain. Measurement of macrophage respiratory burst by chemiluminescence disclosed that T. cruzi infection induced an enhancement of the respiratory burst, no matter the parasite subpopulation employed. But, while in mice surviving RA infection the respiratory burst was higher than during the acute period and parasitaemia was efficiently controlled, in mice infected with K98 enhanced respiratory burst coexisted with measurable levels of parasitaemia either at acute or chronic infection periods. Macrophage activation was also proved by enhanced trypanocidal activity in macrophages derived from mice infected with any of the parasite subpopulations. Sera from RA mice opsonized and lysed T. cruzi bloodstream forms efficiently, whereas sera from CA-I or K98 mice neither lysed nor opsonized this parasite stage. All three subpopulations assayed here showed IgG bound to their membranes in vivo and similar capping kinetics, but only antibodies bound to RA parasites invariably triggered lysis. Therefore, the role played by macrophage activation in resistance and control of Pm levels is related to some features of each T. cruzi subpopulation, such as its capacity to invade macrophages and to elicit opsonizing antibodies.
Subject(s)
Antibodies, Protozoan/immunology , Macrophage Activation/immunology , Opsonin Proteins/immunology , Trypanosoma cruzi/immunology , Animals , Chagas Disease/immunology , Disease Models, Animal , Macrophages/parasitology , Male , Mice , Mice, Inbred C3H , Phenotype , Respiratory Burst/immunologyABSTRACT
Este estudio fue diseñado buscando un método sencillo que permitiera evaluar el compromiso denervatorio o muscular primario en la infección experimental con T. cruzi. Para ello se empleó la exploración electromiográfica convencional de los músculos isquiotibiales de una de las patas en diferentes cepas de ratones infectados con 3 cepas de T. cruzi. Se estudiaron las siguientes asociaciones entre parásitos y huéspedes: Tulahuén (Tul) y C3H/HeN, C57Bl, Balb/c ó Swiss; CA-I y C3H/HeN, Rockland, NIH; RA y C3H/HeN, Rockland. Los ratones se infectaron con tripomastigotes sanguíneos de t. cruzi administrados por vía intraperitoneal. En el electromiograma fueron estudiadas la amplitud, duración y número de fases de los potenciales de undad motora aislados. Se observó que la cepa Tul inducía alteraciones de tipo denervatório en ratones C3H/HeN y C57BI y que igual acontecía con la cepa RA en ratones C3H/HeN. Modificaciones sugestivas de daño muscular primario se vieron en la asociación parásito CA-I y huéspede C3H/HeN y entre CA-I y HIH. La metodología empleada demostró ser de utilidad práctica para la rápida detección del tipo de compromiso de la unidad motora en las infecciones murinas experimentales con T. cruzi (AU)
Subject(s)
Comparative Study , Animals , Male , Mice , Trypanosoma cruzi/pathogenicity , Mice, Inbred Strains/parasitology , Peripheral Nervous System Diseases/parasitology , Chagas Disease/parasitology , Denervation , Electromyography , Injections, Intraperitoneal , Muscles/innervation , Muscles/parasitology , Peripheral Nervous System Diseases/genetics , Species Specificity , Trypanosoma cruzi/classification , Trypanosoma cruzi/growth & development , Virulence , Chagas Disease/genetics , Mice, Inbred Strains/geneticsABSTRACT
Este estudio fue diseñado buscando un método sencillo que permitiera evaluar el compromiso denervatorio o muscular primario en la infección experimental con T. cruzi. Para ello se empleó la exploración electromiográfica convencional de los músculos isquiotibiales de una de las patas en diferentes cepas de ratones infectados con 3 cepas de T. cruzi. Se estudiaron las siguientes asociaciones entre parásitos y huéspedes: Tulahuén (Tul) y C3H/HeN, C57Bl, Balb/c ó Swiss; CA-I y C3H/HeN, Rockland, NIH; RA y C3H/HeN, Rockland. Los ratones se infectaron con tripomastigotes sanguíneos de t. cruzi administrados por vía intraperitoneal. En el electromiograma fueron estudiadas la amplitud, duración y número de fases de los potenciales de undad motora aislados. Se observó que la cepa Tul inducía alteraciones de tipo denervatório en ratones C3H/HeN y C57BI y que igual acontecía con la cepa RA en ratones C3H/HeN. Modificaciones sugestivas de daño muscular primario se vieron en la asociación parásito CA-I y huéspede C3H/HeN y entre CA-I y HIH. La metodología empleada demostró ser de utilidad práctica para la rápida detección del tipo de compromiso de la unidad motora en las infecciones murinas experimentales con T. cruzi
Subject(s)
Animals , Male , Mice , Mice, Inbred Strains/parasitology , Chagas Disease/parasitology , Peripheral Nervous System Diseases/parasitology , Trypanosoma cruzi/pathogenicity , Mice, Inbred Strains/genetics , Denervation , Chagas Disease/genetics , Electromyography , Species Specificity , Injections, Intraperitoneal , Muscles/innervation , Muscles/parasitology , Peripheral Nervous System Diseases/genetics , Trypanosoma cruzi/classification , Trypanosoma cruzi/growth & development , VirulenceABSTRACT
This study has been designed to find an easy method to evaluate the motor unit alterations induced during experimental T. cruzi infections. Different mouse strains infected with three strains of T. cruzi were used to perform conventional needle electromyography, in one of the lower limb hamstring muscles; amplitude, duration and number of phases of single motor unit potentials were measured. The following parasite strain to mouse strain relationship was investigated, in mice inoculated intraperitoneally with bloodstream forms of T. cruzi: Tulahuen and C3H/HeN, C57Bl, Balb/c, Swiss; CA-I and C3H/HeN, Rockland, NIH; RA and C3H/HeN, Rockland. T. cruzi-induced denervating alterations were found in both C3H/HeN and C57Bl mice infected with the Tulahuen strain, as well as in C3H/HeN mice inoculated with the CA-I strain. Moreover, CA-I trypomastigotes could produce primary muscle changes in C3H/HeN and NIH mice. The technique employed in this investigation proved to be an easy and adequate way to detect changes within the motor unit during T. cruzi infection in mice.
Subject(s)
Chagas Disease/parasitology , Mice, Inbred Strains/parasitology , Peripheral Nervous System Diseases/parasitology , Trypanosoma cruzi/pathogenicity , Animals , Chagas Disease/genetics , Denervation , Electromyography , Genetic Predisposition to Disease , Injections, Intraperitoneal , Male , Mice , Mice, Inbred Strains/genetics , Muscles/innervation , Muscles/parasitology , Peripheral Nervous System Diseases/genetics , Species Specificity , Trypanosoma cruzi/classification , Trypanosoma cruzi/growth & development , VirulenceABSTRACT
This study has been designed to find an easy method to evaluate the motor unit alterations induced during experimental T. cruzi infections. Different mouse strains infected with three strains of T. cruzi were used to perform conventional needle electromyography, in one of the lower limb hamstring muscles; amplitude, duration and number of phases of single motor unit potentials were measured. The following parasite strain to mouse strain relationship was investigated, in mice inoculated intraperitoneally with bloodstream forms of T. cruzi: Tulahuen and C3H/HeN, C57Bl, Balb/c, Swiss; CA-I and C3H/HeN, Rockland, NIH; RA and C3H/HeN, Rockland. T. cruzi-induced denervating alterations were found in both C3H/HeN and C57Bl mice infected with the Tulahuen strain, as well as in C3H/HeN mice inoculated with the CA-I strain. Moreover, CA-I trypomastigotes could produce primary muscle changes in C3H/HeN and NIH mice. The technique employed in this investigation proved to be an easy and adequate way to detect changes within the motor unit during T. cruzi infection in mice.
