CYTOKINE REGULATION OF HOST DEFENSE AGAINST PARASITIC GASTROINTESTINAL NEMATODES:Lessons from Studies with Rodent Models^*

Abstract

Studies with rodents infected with Trichinella spiralis, Heligmosomoides polygyrus, Nippostronglyus brasiliensis, and Trichuris muris have provided considerable information about immune mechanisms that protect against parasitic gastrointestinal nematodes. Four generalizations can be made: 1. CD4+ T cells are critical for host protection; 2. IL-12 and IFN-gamma inhibit protective immunity; 3. IL-4 can: (a) be required for host protection, (b) limit severity of infection, or (c) induce redundant protective mechanisms; and 4. Some cytokines that are stereotypically produced in response to gastrointestinal nematode infections fail to enhance host protection against some of the parasites that elicit their production. Host protection is redundant at two levels: 1. IL-4 has multiple effects on the immune system and on gut physiology (discussed in this review), more than one of which may protect against a particular parasite; and 2. IL-4 is often only one of multiple stimuli that can induce protection. Hosts may have evolved the ability to recognize features that characterize parasitic gastrointestinal nematodes as a class as triggers for a stereotypic cytokine response, but not the ability to distinguish features of individual parasites as stimuli for more specific protective cytokine responses. As a result, hosts deploy a set of defense mechanisms against these parasites that together control infection by most members of that class, even though a specific defense mechanism may not be required to defend against a particular parasite and may even damage a host infected with that parasite.

Role of STAT6 and Mast Cells in IL-4- and IL-13-Induced Alterations in Murine Intestinal Epithelial Cell Function

“…STAT6-deficient (STAT6 Ϫ/Ϫ ) mice on a BALB/c background were bred at Uniformed Services University of the Health Sciences (Bethesda, MD), and were age and sex matched with controls in all experiments. 4 …”

“…Gastrointestinal nematode infections, afflicting nearly 1 billion people worldwide (1,2), generally invoke a type 2 cytokine response (3), and are characterized by the production of IL-4, IL-5, IL-6, IL-9, and IL-13 in the infected host (4 -6). Up-regulation of these cytokines results in elevations in serum IgE, eosinophilia, and hyperplasia of mucosal mast cells (MMC) 3 (4) that secrete soluble mediators, including histamine and PGE 2 , which affect epithelial cell function (7)(8)(9)(10)(11).…”

Immunological basis of differences in disease resistance in the chicken

“…On the other hand, the Th2 cytokines such as IL-4, IL-5, IL-6 and IL-10 stimulate the humoral (antibody) response [60]. The differentiation of a progenitor T helper cell into the Th1 or Th2 helper cell has a critical impact on the pattern of immune response and subsequently on disease development [40,54]. The initial priming of the resting T helper cell (Th0) occurs by the cytokines released instantly by phagocytes (macrophages) during infection.…”

Intraepithelial NK Cell-Derived IL-13 Induces Intestinal Pathology Associated with Nematode Infection

“…In addition, there is a marked eosinophilia in response to IL-5 (13) and a pronounced mastocytosis (14). Expulsion of the parasites from the intestine is dependent on mast cells recruited to the mucosa in response to IL-4 and IL-9 (15)(16)(17). Furthermore, there are goblet cell hyperplasia and mucus hypersecretion that may provide mucosal protection for the host or create an inhospitable environment for the parasite (18).…”