concanavalin-a and Influenza--Human

Antigen-presenting cells express pattern recognition receptors (PRRs), which sense pathogen-associated molecular patterns from microorganisms and lead to the induction of inflammatory responses. C-type lectin receptors (CLRs), the representative PRRs, bind to microbial polysaccharides, among which Dectin-2 and Mincle recognize mannose-containing polysaccharides. Because influenza virus (IFV) hemagglutinin (HA) is rich in mannose polysaccharides, Dectin-2 or Mincle may contribute to the recognition of HA. In this study, we addressed the possible involvement of Dectin-2 and Mincle in the viral recognition and the initiation of cytokine production. Interleukin (IL)-12p40 and IL-6 production by bone marrow-derived dendritic cells (BM-DCs) upon stimulation with HA was significantly reduced in Dectin-2 knockout (KO) mice compared to wild-type (WT) mice whereas there was no difference between WT mice and Mincle KO mice. BM-DCs that were treated with Syk inhibitor resulted in a significant reduction of cytokine production upon stimulation with HA. The treatment of BM-DCs with methyl-α-D-mannopyranoside (ManP) also led to a significant reduction in cytokine production by BM-DCs that were stimulated with HA, except for the A/H1N1pdm09 subtype. IL-12p40 and IL-6 synthesis by BM-DCs was completely diminished upon stimulation with HA treated with concanavalin A (ConA)-bound sepharose beads. Finally, GFP expression was detected in reporter cells that were transfected with the Dectin-2 gene, but not with the Mincle gene, when stimulated with HA derived from the A/H3N2 subtype. These data suggested that Dectin-2 may be a key molecule as the sensor for IFV to initiate the immune response and regulate the pathogenesis of IFV infection.

Topics: Animals; Antigen-Presenting Cells; Bone Marrow Cells; Concanavalin A; Cytokines; Disease Models, Animal; Green Fluorescent Proteins; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Immune System; Influenza, Human; Interleukin-12 Subunit p40; Interleukin-6; Lectins, C-Type; Ligands; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; NFATC Transcription Factors; Sepharose; Syk Kinase

This report describes alterations in functional responses to lectin-induced stimulation of peripheral blood lymphocytes and in the natural killer cell (NKC) activity, of college students, obtained during an outbreak of influenza A/Philippines/2/82(H3N2) virus infection. These results are compared with similar observations in college students with an acute, febrile, noninfluenzal respiratory illness that occurred during the same outbreak. The lymphopenia typical of influenza during acute illness was shown to be due to a reduction in both T and B cells without alteration in the CD4:CD8 ratio. In addition, phytohemagglutinin and concanavalin A responses were reduced and NKC activity was increased, while pokeweed mitogen reactivity was unaltered at the time of admission to the study. Patients with noninfluenzal illness showed early polymorphonuclear leukocytosis and a similar lymphopenia. Lymphocyte functions were virtually unchanged during acute illness in noninfluenza patients. The relatively specific alterations in lymphocyte responses to lectin-induced stimulation in influenza patients may indicate that the peripheral T cells are incapable of activation via the CD3 or CD2 activation pathways. In addition, increased NKC activity in the periphery may be reflective of increased NKC activity in the lung. Influenza-infected individuals with higher NKC activity at the time of admission to the study also took longer to recover. Finally, the early lymphopenia and the later neutropenia in the influenza-infected patient may represent migration of these cells from the circulation to the infected respiratory tract as a consequence of infection.

Topics: Concanavalin A; Humans; Influenza A virus; Influenza, Human; Interferons; Killer Cells, Natural; Lymphocyte Activation; Lymphocytes; Lymphopenia; Phytohemagglutinins; Pokeweed Mitogens; Respiratory Tract Infections

We have described in this paper a novel human interferon (IFN) with antigenic and cross-species reactivity of alpha-IFN and physicochemical properties of gamma-IFN. This IFN is produced by normal peripheral blood mononuclear cells during an immune response but has also been associated with autoimmune disease (10). The system described here will be useful in elucidating the biological significance and cell of origin of this IFN.

Topics: Animals; Cattle; Concanavalin A; Cross Reactions; Haplorhini; Humans; Hydrogen-Ion Concentration; Influenza A virus; Influenza Vaccines; Influenza, Human; Interferon Type I; Lymphocyte Activation; Lymphocytes

Topics: Animals; Antilymphocyte Serum; Binding Sites, Antibody; Binding, Competitive; Concanavalin A; Fluorescent Antibody Technique; Humans; Influenza, Human; Interleukin-2; Isoantibodies; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Phytohemagglutinins; Rats; T-Lymphocytes, Cytotoxic

Cell-mediated immune responses were examined in 19 normal volunteers after intranasal administration of three strains of influenza A virus. Eight volunteers manifested respiratory tract illness along with fourfold rises of serum antibody and/or virus shedding. Samples of peripheral venous blood were obtained before and two days, five days, and four weeks after challenge. During acute illness, infected volunteers showed lymphopenia, which persisted for up to four weeks after challenge. The lymphopenia involved thymus-derived, bone marrow-derived, and null cells. Blastogenic responses of lymphocytes to stimulation with phytohemagglutinin, concanavalin A, and streptokinase-streptodornase were depressed during acute illness, and responses to phytohemagglutinin and concanavalin A remained depressed at four weeks after infection. Thus, influenza infection in humans can result in prolonged depression of numbers and functions of circulating lymphocytes.

Topics: Adolescent; Adult; Antibodies, Viral; B-Lymphocytes; Cells, Cultured; Concanavalin A; Humans; Immunity, Cellular; Influenza A virus; Influenza, Human; Lectins; Lymphocyte Activation; Lymphopenia; Mitogens; Streptodornase and Streptokinase; T-Lymphocytes