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Parasitological and immunological interactions between Eimeria vermiformis or E. pragensis and Trichinella spiralis were investigated during concurrent infections in NIH, BALB/c and B10.G inbred mice. The establishment of T. spiralis was unaffected by the presence of either coccidium, but expulsion of adult worms was delayed significantly in mice infected with E. vermiformis; E. pragensis did not have this effect. Replication of E. vermiformis was enhanced in concurrent infections with T. spiralis, but that of E. pragensis was reduced. Specific immune responses to each parasite were unaffected in mice infected with T. spiralis and E. pragensis, but levels of some responses were reduced when T. spiralis and E. vermiformis were combined. Thus both in vitro antigen-induced proliferation of mesenteric lymph node cells (MLNC) and intestinal mastocytosis were lower than in singly infected mice. Mitogen (Con A) responsiveness of MLNC was not affected in mice infected with T. spiralis and E. vermiformis, and cells from these mice were capable of transferring protective immunity to the nematode in naive recipients. Injection of monoclonal antibody to interferon gamma, a major component of the cytokine response to E. vermiformis, did not prevent delay of worm expulsion in concurrent infections. The results are discussed in terms of possible interactions between the T helper cell subsets or the inflammatory components of the responses induced by each parasite.

In electron microscopic studies on structure of the capsule surrounding Trichinella spiralis larva the techniques have been employed which permit demonstration of proteoglycans and collagen fibers at various stages of their formation, i.e. fixation in tannic acid and staining reaction with ruthenium red. The muscle cell has been demonstrated to produce both collagen fibers and glycoproteins plus proteoglycans. The products formed inner part of the capsule, separated from the outer part by the basement membrane. The outer part of the capsule contained collagen fibers and matrix, synthesized by the interstitial tissue cells, by fibroblasts and vascular endothelium cells in particular.

Parasites exploit the environment provided by their hosts in the same way that free-living animals exploit their physical and biotic environments. There is, however, 1 important difference: the host environment can respond adaptively to infection in ways that may be disadvantageous to the parasite. Immunity provides the most effective adaptive host response and exerts a major selective pressure in parasite evolution. Among parasites many ways of maintaining the ability to exploit the host in the face of adaptive responses have evolved; such responses additionally may promote survival by enhancing transmission. The nematode Trichinella spiralis provides an excellent model with which to explore immuno-parasite-ecological ideas. Its biology is well known, and host immunity is described in detail. Immunity acts to limit parasite survival, but it also helps to ensure transmission by allowing the host to survive until infective stages mature. Host and parasite engage in a complex interplay, mediated by immunity, in which the genetic variability of each partner plays an important and necessary role.

Trichinella spiralis is an intracellular parasite as both a larva and an adult. The first-stage larva lives in a modified portion of a skeletal muscle cell, the nurse cell, and can reside there for the life span of the host. Adult worms occupy a nonmembrane-bound portion of columnar epithelium, living there as intramulticellular parasites. The newborn larva is the only nonintracellular stage, living free in the circulation. Trichinella spiralis induces modifications in each of its intracellular niches. Parasite signals secreted into the milieu of the developing nurse cell results in the reprogramming of host genomic expression, reflected in loss of muscle-specific proteins, over-expression of collagen, and the development of a circulatory rete. Formation of the nurse cell is complex, presumably involving many steps; yet there is not a large series of related intermediate forms in nature. Trichinella pseudospiralis induces an incomplete nurse cell. Adult parasites cause the death of the infected epithelium. The precise nature of most of the signals from parasite to host and from host to parasite has not been determined. As a direct consequence of exposure to some of them, the host develops long-lasting immunity to reinfection. This may confer advantages both for the parasite, as well as the host, because strong immune responses should reduce intraspecific competition.

Weaned rats were passively immunized with rat IgG2c monoclonal antibodies previously shown to protect infant rats against challenge with Trichinella spiralis. Although the antibodies did not protect rats against infection, the course of larval establishment in the intestine was altered in a way that has not been described previously. Specifically, larvae that invaded the epithelium were inhibited from migrating from intestinal tissue into saline during the standard recovery procedure. The inhibition was reversed at a time coincident with the first moult. Whole serum from infected rats had a similar effect. These results show that specific antibodies influence T. spiralis larvae in the intestinal epithelium, yet fail to effect their expulsion from adult rats.

Infection by Trichinella spiralis causes a variety of changes in skeletal muscle cells including the hypertrophy of nuclei and decreased expression of muscle specific proteins. Potential cellular processes leading to these changes were investigated. In synchronized muscle infections, [3H]thymidine was incorporated into infected cell nuclei from 2-5 days post infection. Labeled nuclei were stably integrated into the infected cell up to 60 days post infection and appear to originate from differentiated skeletal muscle nuclei present at the time of infection. These nuclei were further shown to contain a mean DNA content of approximately 4N, indicating that the [3H]thymidine uptake reflects DNA synthesis and subsequent long-term suspension of the infected cell in the cell cycle at G2/M. Associated with these changes, muscle specific gene transcripts were reduced to < 1- < 0.1% in the infected cell compared to normal muscle. Transcript levels of the muscle transcriptional regulatory factors myogenin, MyoD1, and Id were reduced to < 10, < 1, and increased approximately 250%, respectively, in the infected cell compared to normal muscle, indicating transcriptional inactivation of muscle genes. DNA synthesis in the infected cell may represent the initiation event which leads to expression of this infected cell phenotype.

The effect of oral immunization and the adjuvancy of cholera toxin (CT) were examined in mice infected with Trichinella spiralis. The mean of total muscle larvae was reduced by 36% in mice infected with Trichinella larvae in combination with CT. In mice fed soluble, particulate, or soluble/particulate antigens in combination with CT on Days 0, 14, and 21, and challenged with Trichinella larvae on Day 28, there was a significant reduction in adult worm fecundity (50%), worm size (20-30%), and the mean of total muscle larvae (75%) but no apparent effect on the rate of expulsion on Day 6 postchallenge. Following antigen feeding, but prior to challenge with Trichinella (Day 28), the immunoglobulin response was positive in only a small proportion of mice. On Day 6 following challenge with Trichinella larvae, the biliary immunoglobulin response was enhanced approximately 10-fold (P < 0.05) in all antigen-feeding treatments which included CT, compared with nonimmunized controls or antigen-feeding treatments which did not include CT. Similarly, the serum IgG response was enhanced following challenge with Trichinella larvae in treatments fed soluble, particulate, or soluble/particulate antigens with CT. The response was also enhanced in the particulate, but not in soluble or soluble/particulate antigen treatments without CT.