Infection cytokine type 2 response

It is clear that the type 2 cytokines IL-4, IL-9 and IL-13 play an obligatory role in host resistance to nematode infection whereas type 1 responses promote host susceptibility. Therefore, given that susceptibility to nematode infection is not due to a lack of responsiveness perse, but rather the development of an inappropriate response, it is important to understand the factors that influence the induction and expansion of Th subset responses and so control infection outcome. Studies in nematode models and other systems have addressed these questions and identified the importance of host genetic factors, the nature of the antigen and the antigen presenting cell, co-stimulatory molecules on these cells, and the cytokine and chemokine environment immediately following induction of the response. 

Respiratory syncytial virus (RSV) infection is a major cause of bronchiolitis in infants, whereas influenza A infection usually manifests as an upper respiratory tract infection. The immunological responses of infants to RSV infection and influenza A infection are different. In our studies of the cytokine responses during these infections, we found that the serum concentrations of IL-4, IL-5, RANTES, and soluble intercellular adhesion molecule-1 (sICAM-1) in infants with RSV infection were significantly higher than those with influenza A infection (S8). The concentration of TNF-a in nasopharyngeal aspirates was significantly lower in infants with RSV infection. Therefore, a predominant T helper cell type 2 (Th2) cytokine and related immunological response was observed in infants with RSV infection, whereas a predominantly proinflammatory cytokine response was observed in infants with influenza A infection. This may explain the different clinical manifestations of the two viral infections in infants (S8). 

Innate immune response to viral infections is predominately through interferon-alpha, -beta (IFN-a and -P) induction and activation of natural killer (NK) cells. Although viral replication can induce IFN-a and -P expression, macrophages are capable of producing and secreting cytokines which also induce the production of these type I interferons (Falk 2001). Bound IFNa and p to its receptors on NK cells increases its ability to lyse virally-infected cells. 

T cells control these learned responses and decide which tools to use in the reaction. Sometimes they choose several different tools at once, and multiple reactions ensue, such as when a person becomes sensitized to penicillin and has not only anaphylaxis but hemolytic anemia and serum sickness. There are different types of T cells, and they communicate either directly with other cells or by chemical messages called cytokines. The pattern of cytokines released is one way T cells have of determining which kind of response will occur. They are broadly called Thl andTh2 responses, with Thl mostly responding to infections and Th2 often producing allergy or asthma. 

Interferon-y (IFN-y) mRNA levels were measured in unstimulated peripheral blood mononuclear cell (PBMC) and purified cell populations, using a bDNA assay, to characterize the cell types that contribute to the in vivo increase in IFN-y gene expression seen in HIV infection (Breen et al 1997). IFN-y is a cytokine that can be produced by multiple cell types and is considered to enhance cellular responses by activation of monocytes and macrophages. It is one of the type 1 cy-... 

The in vivo manipulation of specific type 2 cytokines using anticytokine monoclonal antibodies, or mouse strains with targeted deletions in cytokine and/or cytokine receptor genes, has proved a fruitful approach in identifying the importance of individual cytokines and the responses that they control in contributing to host resistance. These studies have identified important roles for IL-4, IL-9 and IL-13 in host protection against nematode infection, though the relative importance of each cytokine appears to be nematode-species dependent. 

IL-13 KO mice failed to clear infection despite mounting equivalent type 2 cytokine responses to wild-type mice. Further evidence of a role for IL-13 in expulsion is shown in studies utilizing BALB/c IL-4 KO mice. While control mice cleared infection, treatment with A25 (a soluble IL-13 receptor alpha 2-human IgG-Fc fusion protein) prevented worm expulsion. (Data adapted from Bancroft et al., 1998 A.J. Bancroft, unpublished.)... 

A variety of type 2 cytokines and the non-lymphoid cell-derived growth factor, stem cell factor (SCF) (Hiiltner et al., 1989 Copeland et al., 1990 Huang et al., 1990 Thompson-Snipes et al., 1991 reviewed in Befus, 1995), are known to be important in the development of intestinal mast cell responses associated with nematode infection but the contribution of this population to host protection depends on the nematode species in question. 

It is also more or less accepted that T-cells, in particular T-helper cells (CD4+), may develop into either Thl cells or Th2 cells. By doing so, T-helper cells orchestrate the ensuing immune response by the types of cytokines they produce. Thl cells, by producing IL-12 and y-IFN, stimulate macrophages and/or cytotoxic T-cells to kill and destroy infected or malignant cells, or to initiate a delayed type hypersensitivity (DTH) reaction Th2 cells, by producing IL-4, IL-5, IL-10, IL-13, trigger B-cells to initiate antibody production. 

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