asialo-gm1-ganglioside and Pneumonia

The cell-mediated immune response has been documented to be the major protective immune mechanism in mice infected genitally with the agent of mouse pneumonitis (MoPn), a biovar of Chlamydia trachomatis. Moreover, there is strong evidence to indicate that gamma interferon (IFN-gamma) is a major effector mechanism of the cell-mediated immune response. Previous studies from this laboratory have also reported that the dominant cell population in the genital tract is the CD4 Th1 population. When experiments were performed by the enzyme-linked immunospot assay, high numbers of cells producing IFN-gamma were found in the genital tract, concomitant with resolution of the infection; however, in addition, an increase in IFN-gamma-producing cells which were CD4(-) was seen early in the infection. Since natural killer (NK) cells produce IFN-gamma and have been found to participate in the early responses in other infections, we hypothesized that NK cells are responsible for early IFN-gamma production in the murine chlamydial model. NK cells were quantified by the standard YAC-1 cytotoxicity assay and were found to appear in the genital tract as early as 12 h after intravaginal infection with MoPn. The cells were confirmed to be NK cells by abrogation of YAC-1 cell cytotoxicity by treatment in vitro and in vivo with anti-asialo-GM1. The early IFN-gamma response could also be depleted by treatment with anti-asialo-GM1, indicating that NK cells were responsible for the production of this cytokine. Of interest was our observation that depletion of NK cells also exacerbated the course of infection in the mice and elicited a Th2 response, as indicated by a marked increase in immunoglobulin G1 antibody. Thus, these data demonstrate that NK cells are not only responsible for the production of IFN-gamma early in the course of chlamydial genital tract infection but are also, via IFN-gamma, a significant factor in the development of the Th1 CD4 response and in the control of the infection.

Topics: Animals; Chlamydia Infections; Chlamydia trachomatis; Cytokines; Female; G(M1) Ganglioside; Genitalia, Female; Ilium; Immunoglobulin G; Immunoglobulin Isotypes; Interferon-gamma; Killer Cells, Natural; Lymph Nodes; Lymphocyte Depletion; Mice; Mice, Inbred BALB C; Pneumonia; Rodent Diseases; Th1 Cells; Vaginal Diseases

Pneumonia is one of the most common causes of death from infectious disease in the United States. To examine the possible role of carbohydrates as adhesion receptors for infection, several pulmonary pathogenic bacteria were studied for binding to glycosphingolipids. Radiolabeled bacteria were layered on thin-layer chromatograms of separated glycosphingolipids, and bound bacteria were detected by autoradiography. The classic triad of infectious bacteria found in cystic fibrosis, Pseudomonas aeruginosa, Haemophilus influenzae, and Staphylococcus aureus, along with other bacteria commonly implicated in typical pneumonia, such as Streptococcus pneumoniae, Klebsiella pneumoniae, and certain Escherichia coli, bind specifically to fucosylasialo-GM1 (Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Cer), asialo-GM1 (Gal beta 1-3GalNAc beta 1-4Gal beta-1-4Galc beta 1-1Cer), and asialo-GM2 (GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer). Bacteria maintained in nutrient medium bind better than the same cells suspended in buffer. They do not bind to galactosylceramide, glucosylceramide, lactosylceramide, trihexosylceramide, globoside, paragloboside, Forssman glycosphingolipid, or several other glycosphingolipids tested, including the gangliosides GM1, GM2, GM3, GD1a, GD1b, GT1b, and Cad. The finding that these pathogens do not bind to lactosylceramide suggests that beta 1-4-linked GalNAc, which is positioned internally in fucosylasialo-GM1 and asialo-GM1 and terminally in asialo-GM2, is required for binding. beta-N-Acetylgalactosamine itself, however, is not sufficient for binding, as the bacteria did not bind to globoside, which contains the terminal sequence GalNAc beta 1-3Gal. These data suggest that these bacteria require at least terminal or internal GalNAc beta 1-4Gal sequences unsubstituted with sialyl residues for binding. Other bacteria, including Mycoplasma pneumoniae, Streptococcus pyogenes, Salmonella species, and some E. coli, do not bind to the GalNAc beta 1-4Gal sequence. The biological relevance of these data is suggested by our finding that substantial amounts of asialo-GM1 occur in human lung tissue.

Topics: Animals; Bacteria; Bacterial Adhesion; Carbohydrate Metabolism; Carbohydrate Sequence; G(M1) Ganglioside; Glycosphingolipids; Humans; Lung; Mice; Pneumonia