Comparison of cytotoxic and microbicidal function of bronchoalveolar and peritoneal macrophages.

Studies were carried out with mice to explore in vitro the effector function(s) of macrophages from two different anatomical compartments (peritoneal cavity and lungs). The cytotoxic capacity of macrophages was measured by determining their cytostatic and cytocidal effects on EL-4 tumour target cells, and the microbicidal capacity of macrophages was measured by determining their ability to kill or inhibit the intracellular protozoan, Toxoplasma gondii. Neither peritoneal macrophages (PM) nor bronchoalveolar macrophages (BAM) from normal mice were ever microbicidal or cytotoxic. Intravenous treatment with Corynebacterium parvum greatly enhanced (activated) both effector functions of PM but did not activate BAM. Chronic infection with Toxoplasma activated PM throughout the period of observation (greater than 140 days), but the presence of activated BAM was transient and appeared to coincide with the occurrence of an inflammatory response in the lungs.

Toxoplasmosis presenting as brain abscesses. Diagnosis by computerized tomography and cytology of aspirated purulent material.

A patient with brain abscesses caused by Toxoplasma gondii is described. Presence of brain abscesses was confirmed by computerized tomography, and T. gondii was identified as the etiologic agent in cytologic preparations of aspirated purulent material from one of the abscesses.

Cryptosporidial enteritis in a patient with congenital hypogammaglobulinemia.

Cryptosporidium is a potentially pathogenic coccidial protoxoan known to inhabit the striated border of interestinal epithelium in several animal species. Recently two cases of human intestinal cryptosporidiosis have been described. The purpose of this report is to document a third case of chronic debilitating cryptosporidial enteritis in a young boy with congenital hypogammaglobulinemia. The endogenous protozoan life cycle and morphologic features are examined as studied by light and electron microscopy.

Probable transmission of Toxoplasma gondii by organ transplantation.

Two heart transplant recipients developed toxoplasmosis shortly after surgery. As neither recipient had serologic evidence of exposure to Toxoplasma gondii before transplantation, infection was acquired from an exogenous source. Of the possible modes of transmission of Toxoplasma to the recipients, infection by the oral route or through transfusion of blood or blood products seems remote. Since both heart donors had serologic evidence of recently acquired toxoplasma infection at the time of transplantation and the myocardium is known to be infected with the organism during acute infection, we considered these facts to be a strong implication that the donors' hearts were the most likely source of toxoplasma infection in the recipients.

Pneumocystis carinii, Toxoplasma gondii, Cytomegalovirus and the compromised host.

Pneumocystis carinii and Toxoplasma gondii are the two major parasitic protozoan pathogens in the immunocompromised host. Both organisms cause latent infection in humans and many animals. Cats are the definitive hosts for toxoplasmosis; the animal vector for pneumocystis (if any) has not been defined. Toxoplasma is an obligate intracellular parasite, whereas the available evidence suggests that Pneumocystis carinii exists primarily extracellularly. In compromised hosts, pneumocystis infection usually involves only lungs, whereas toxoplasma causes a generalized infection with encephalitis being the principal clinical manifestation. Both types of infection are treated with combinations of folate antagonists (trimethoprim or pyrimethamine with sulfonamide). Both parasites are associated with cytomegalovirus infection in immunosuppressed hosts, an association which may be due to symbiosis between parasites, or to an additive immunosuppressive effect of dual infection on the hosts.

Effect of cytochalasin D on Toxoplasma gondii cell entry.

Cytochalasin D did not prevent attachment but did prevent entry of Toxoplasma gondii into peritoneal macrophages and bladder tumor 4934 cells. Inhibition of entry of T. gondii into peritoneal macrophages by cytochalasin D was dose related and comparable to inhibition of phagocytosis. Prevention of entry of T. gondii into bladder tumor 4934 cells by cytochalasin D followed a dose response identical to that observed with peritoneal macrophages. After removal of the medium containing cytochalasin D, its effect was completely reversible, and the kinetics of the loss of inhibition followed a similar time course for both phagocytic and "nonphagocytic" cell types. The studies support the concept that the host cells actively participate in the process by which T. gondii gains entry into cells.

Effect of alveolar macrophages on Toxoplasma gondii.

As pulmonary involvement can occur in disseminated toxoplasmosis in immunosuppressed patients, studies were initiated to define local mechanisms of resistance of the lung to Toxoplasma gondii. Alveolar macrophages were obtained from normal mice and mice chronically infected with T. gondii by bronchopulmonary lavage and cultured in vitro. Although normal alveolar macrophages were difficult to infect with Toxoplasma, they supported intracellular multiplication of this organism. When exposed to Toxoplasma that had been pretreated with heat-inactivated serum containing specific antibody, the number of intracellular organisms increased remarkably, and the macrophages destroyed the coated parasites. After development of chronic infections with Toxoplasma, there was a transient period during which a striking increase in numbers of alveolar macrophages was observed in lavage specimens. These macrophages differed from those of normal alveolar macrophages. There was a greater percentage of large cells, a greater tendency to spread on glass, and an increased number of intracellular Toxoplasma, and the cells were activated to kill or inhibit multiplication of the parasite. During the period when activated macrophages were demonstrable in bronchopulmonary washings, histological changes in the lungs revealed a marked mononuclear cell infiltrate. These studies support a role for the activated alveolar macrophage as an effector in resistance of the lung to infection with Toxoplasma.