The Importance of Th2 Cytokines in Protective Immunity to Nematodes

Urban, Joseph F.; Madden, Kathleen B.; Svetica, Antonela; Cheever, Allen W.; Trotta, Paul P.; Gause, William C.; Katona, Ildy M.; Finkelman, Fred D.

doi:10.1111/j.1600-065x.1992.tb01415.x

Cited by 326 publications

(224 citation statements)

References 63 publications

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“…In general, the patterns of differential expression indicated a complex response to GI nematodes and no apparent single pathway related to resistance. In addition, immune responses were of both the TH1 and TH2 types, which differs from studies in rodents that indicate resistance to GI nematodes is related to a TH2 response (Urban et al, 1992). In a second study of this selected cattle population, evaluated expression of 17 cytokines and cytokine receptors by qRT-PCR in five GI tissues of resistant and susceptible animals in response to a combined Ostertagia ostertagi and Cooperia oncophora challenge.…”

Section: Connor LI Baldwin and Limentioning

confidence: 93%

Gene expression in the digestive tissues of ruminants and their relationships with feeding and digestive processes

Connor

Baldwin

et al. 2010

Animal

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The gastrointestinal tract (GIT) has multiple functions including digestion, nutrient absorption, secretion of hormones and excretion of wastes. In the ruminant animal, development of this organ system is more complex than that of the monogastric animal due to the necessity to establish a fully functional and differentiated rumen, in which a diverse microbial population of bacteria, fungi and protozoa support fermentation and digestion of dietary fiber. Central to the goal of animal scientists to enhance nutrient uptake and production efficiency of ruminants is the need for a comprehensive understanding of GIT development, as well as conditions that alter the digestion process. The relatively recent availability of genome sequence information has permitted physiological investigations related to the process of digestion for many agriculturally important species at the gene transcript level. For instance, numerous studies have evaluated the expression of ruminant GIT genes to gain insight into mechanisms involved in normal function, physiology and development, such as nutrient uptake and transport across the epithelial cell barrier throughout the alimentary canal, maintenance of rumen pH, and regulation of GIT motility and cell proliferation. Further, multiple studies have examined the effects of dietary modification, including feeding of supplemental fat, starch and protein, or a forage-v. concentrate-based diet on expression of critical gene pathways in the gut. In addition, the expression of genes in the GIT in response to disease, such as infection with gastrointestinal parasites, has been investigated. This review will summarize some of the recent scientific literature related to the gene expression in the GIT of ruminants, primarily cattle, sheep and goats, as it pertains to normal physiology, and dietary, developmental, and disease effects to provide an overview of critical proteins participating in the overall digestive processes, and their physiological functions. Recent findings from our laboratory will be highlighted also related to expression of the glucagon-like peptide two-hormone pathway in the GIT of dairy cattle during in various stages of the development and lactation, alterations in gene pathways associated with the rumen development and differentiation in the weaning calf, and genes of the GIT responding to Ostertagia, a common nematode infection of the cattle. Finally, prospective areas of investigation will be highlighted.

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Section: Connor LI Baldwin and Limentioning

confidence: 93%

Gene expression in the digestive tissues of ruminants and their relationships with feeding and digestive processes

Connor

Baldwin

et al. 2010

Animal

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“…The high levels of IL-5 in Mf ¹ subjects could be associated with the strong eosinophilia (>30%, data not shown) encountered in loiasis patients. In fact, IL-5 promotes the terminal differentiation of committed eosinophil precursors [23] and enhances the effector capacity of mature eosinophils [24], which have been shown to act as effector cells in antibody-dependent cellular cytotoxicity (ADCC) against certain helminth infections [18,19], including Loa loa. The strong Th2-type responses in Mf ¹ patients may result from the chronicity of the infection and may be enhanced by IL-2, at the level of IL-4 [25] and IL-5 [26] production.…”

Section: Numerous Studies Concerning Humoral Immune Responses Duringmentioning

confidence: 99%

T helper responsiveness in human Loa loa infection; defective specific proliferation and cytokine production by CD4+ T cells from microfilaraemic subjects compared with amicrofilaraemics

Baize

Wahl

Soboslay

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe proliferation and cytokine profiles of peripheral blood mononuclear cells (PBMC) from microfilaraemic (Mf þ ) subjects infected by Loa loa in response to antigens of several parasitic stages were compared with those from amicrofilaraemic (Mf ¹ ) individuals. While a strong lymphoproliferative response and consistent levels of both Th1 (IL-2, interferon-gamma (IFN-g)) and Th2 (IL-4, IL-5) type cytokines were observed in response to adult worm (AW) and microfilariae (Mf) antigen in Mf ¹ individuals, Mf þ subjects were characterized by a T cell unresponsiveness, including proliferation, cytokine production and IL-2 mRNA expression. Conversely, T cell responsiveness to mitogens and non-specific antigen were similar in the two endemic populations. Depletion of lymphocyte subpopulations indicated that T CD4 þ were mainly involved in the specific cellular response. In contrast to other cytokines, IL-10 was produced in response to all parasitic stages, in both Mf þ and Mf ¹ patients. Neutralization of IL-10 did not restore cytokine production in Mf þ patients, while B7 mRNA expression was similar between Mf þ and Mf ¹ subjects in response to Mf antigen, suggesting that IL-10 was not the only factor responsible for T cell unresponsiveness. Mf þ patients have lower Mf antigen-specific IgG levels compared with Mf ¹ , and there is a significant correlation between Mf antigen-specific antibodies and IL-5 responses. These findings suggest that Mf ¹ status is correlated with T helper responsiveness, including proliferation and production of both Th1-and Th2-type cytokines, whereas Mf þ status is characterized by unresponsiveness of the same cell population, induced and/or maintained by microfilariae.

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“…IL-10 is one of the cytokines belonging to Th2 subset that inhibits the cytokine produced by Thl cells. The role of IL-10 in the downregulation of antigen responsiveness in parasitic infections has been reported in filariasis by us and in other parasitic infections (5,7,10,11).…”

Section: Cytokine Profile In Different Clinical Groups Of Filariasis mentioning

confidence: 53%

“…(Figs 1 and 3). In established murine Schistosomiasis, infection correlates with Th2 response while protective immunity induced by vaccination with irradiated cercaria correlates with elevated Thl cytokine production and is partially ablated by treatment of the vaccinated mice with monoclonal antibodies against IL-2 receptor and I FN-y (10,12). Thus in parasitic diseases Th2 type cytokine production generally leads to progressive and persistent infection and Thl type of cytokine production leads to resistance to parasitic infection.…”

Section: Cytokine Profile In Different Clinical Groups Of Filariasis mentioning

confidence: 99%

“…This non-tolerant condition is associated with normal T-cell proliferative response and lymphatic pathology seen in chronic patients. The mechanism involving the shift in response towards Th2 predominance in helminth infection is unclear but such a shift could result from structural elements in helminth derived antignes or from the chronic antigenic load that occur in helminth infection (10,12).…”

Section: Cytokine Profile In Different Clinical Groups Of Filariasis mentioning

confidence: 99%

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Modulation of cellular immune response by cytokines in bancroftian filariasis

Ravichandran

Regunathan

Narayanan

et al. 1997

Indian J Clin Biochem

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Human lymphatic filariasis is a chronic helminth infection caused by Wuchereria bancroffi and Brugia malayi. Wide spectrum of clinical manifestations are seen in different clinical groups of filariasis patients which comprises asymptomatic patients with circulating microfilaria (MF), individuals with chronic lymphatic obstruction (CP), Endemic normals (EN) who are asymptomatic and amicrofilaraemic or the relatively rare tropical pulmonary eosinophilia (TPE). The cellular immune response to this infection varies in different clinical groups of filarial patients, ranging from normal lymphocyte proliferative response in EN individuals to lymphocyte hyporesponsiveness in MF to total parasite antigen [Brugia malayi antigen (BMA)]. But in response to recombinant filarial antigen (pRJ51) the lymphocyte proliferation is restored in MF patients. Interestinglythe lymphocytes from MFs responded normally to parasite antigen when EN serum was added in the culture whereas serafrom MFsfailed to revert the lymphocyte hyporesponsiveness. In order to study the molecular mechanisms responsible for parasite antigen specific lymphocyte hyporesponsiveness, we analysed both the Thl and Th2 type cytokine gene expression profile in different clinical groups of filarasis patients. MF individuals expressed elevated Th2 type cytokines like IL-4, IL-5 and IL-10 and decreased levels of IL-2 and IFN-7 in response to parasite antigen. Chronic patients have elevated levels of both Thl and Th2 type cytokines in response to parasite antigen. The EN individuals had a purely Thl type pattern with absence of IL-4 and IL-5 expression. These studies clearly demonstrate the role ofTh2 cytokine like ILl0 in antigen specific hyporesponsiveness seen in MF patients. Any methods to arrest the progression of this disease should concentrate on the means to revert the Th2 type into Thl type response in the MF patients either by Thl type cytokine therapy or by using recombinant filarial antigen which stimulates the Thl response. Further the recombinant filarial antigen which induces Thl type cytokine response could be used for immunoprophylactic studies.

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The Importance of Th2 Cytokines in Protective Immunity to Nematodes

Cited by 326 publications

References 63 publications

Gene expression in the digestive tissues of ruminants and their relationships with feeding and digestive processes

Gene expression in the digestive tissues of ruminants and their relationships with feeding and digestive processes

T helper responsiveness in human Loa loa infection; defective specific proliferation and cytokine production by CD4+ T cells from microfilaraemic subjects compared with amicrofilaraemics

Modulation of cellular immune response by cytokines in bancroftian filariasis

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