The T helper cells produced type 1 cytokines IFN-γ, lymphotoxin and IL-2; stimulated IgG2a production and cell mediated effector responses. The type 2 cytokines IL-4, IL-5, IL-6, IL-9 and IL-13 were secreted by Th2 cells in absence of type 1 cytokines and promoted production of IgE and IgG1. Resistance to intestinal nematodes was associated with the development of a Th2 response. A Th2 cytokine response was produced when mouse strains were resistant to Trichuris muris, moreover susceptible strains were associated with a Th1 response. Restimulation of MLNC isolated from resistant (BALB/K) and susceptible (B10.BR) and measurement of IL-5 and IFN-γ production was carried out. Resistant mice displayed high levels of IL-5 and low levels of IFN-G and susceptible the caonverse. Further studies looked at IL-3, IL-4, IL-5 and IL-9 all higher in the BALB/K mice strain. IFN-γ was associated with susceptibility; IgG1 levels were higher in resistant strains and IgG2a in susceptible. Resistant mice which received a short term treatment with cortisone produced Th1 cytokines. Antigen load was important in Th2 response and hence in a low dose infection there were not sufficient levels of antigen available to polarize immune response such that it is protective. In the larval stages parasite got easily expelled but in adulthood chronic infection developed and worms became difficult to expel.


Chemokines are a type of cytokine with chemoattractive properties responsible for migration of lymphocytes to different tissues and compartments within organs. Chemokines were thus important for directing immune response in many diseases like Trichuris muris. Epithelial cells were a source of chemokines and also expressed chemokine receptors. Chemokines CCLII and CCL24 directly recruited IL-5 driven eosinophils. The migration of NK cells into lymph nodes and tissue sites were dependent on CXCR3 expressed. On the other hand, migration of Th1 cells in to tissues depended on IFN-g induced CXCL10 production, a ligand for CXCR3. These were important for recruitment of lymphoid cells to target tissues.

Effector mechanisms of worm expulsions

Trichuris muris infection is characterized by crypt hyperplasia, eosinophilia, goblet cell hyperplasia and mucosal mastocytosis. Mast cells, eosinophils and antibodies are not needed to expel Trichuris muris but it is said that the other mechanisms may play a role but however their function is yet to be elucidated.

Mast cells and Eosinophils

These were thought to play a role in expulsion of worms. When antibody was administered in vivo it helped to reduce mast cell differences and numbers but this failed to expel of parasite. Increase in eosinophils in intestine of resistant mice was seen and their production was under the control of IL-5. Following ablation of IL-5 and hence eosinophilia, mice usually were resistant to Trichuris muris infection remained so. The complete ablation of mast cells over the period of parasite expulsion in resistant mice was done using c-kit which had no effect on the development of protective immunity. Hence it can be seen that mast cells and eosinophils are not critical in resistant.

Goblet cells (GCs)

IL-13 may act by modulating goblet cell differentiation and activation during Trichuris muris infection as it was shown that IL-13 KO mice fail to mount the dramatic goblet cell hyperplasia seen in wild type during expulsion of N. brasiliensis. GCs in the colon secrete mucins that hydrate and form a protective blanket over the epithelial cells of the gut and thus provide a physical barrier to insult. High levels of secretion may act to trap parasites in the gut and minimize their ability to penetrate into the host epithelium. MuC2 is a mouse secreted mucin found mostly in the GI tract. Recently Gob-5 (apical calcium activated chloride channel) has been identified in intestinal epithelium, especially in goblet cells. Only a limited number of proteins secreted by goblet cells were identified like RELMβ (resistin-like molecule) and expression was up regulated on nematode infection. Trichuris muris infection expression was controlled by Th2 cytokines and was coincident with host protective immunity unless they were treated with rIL-13. RELM-β may impair chemosensory functions of gastrointestinal nematodes as it was associated with chemosensory components of the bacillary band thereby hypothetically contributing to their expulsion from gut

Other Mechanisms of expulsion


For many gut nematode infections, "conventional" immune effector mechanisms do not play a major role in worm expulsion. The intestinal epithelium undergoes continuous and rapid renewal; stem cells at the base of the crypts, the epithelium proliferate and give rise to daughter cells which migrate up and differentiate into special epithelial cells like GCs. Chronic Trichuris muris infection was associated with increased epithelial stem cell proliferation within crypts of the large intestine. Along with these there are slow rate of turnover both of which contributed to the observed crypt cell hyperplasia seen in susceptible mice. During the worm expulsion period in resistant mice the turnover was increased compared to the susceptible mice and it was thought that this was enough to displace worms from their niche and help in expulsion. Increase in epithelial turnover in SCID mice was enough to reduce worm burden significantly even in presence of acquired immune response, showing physical displacement of worms was sufficient for expulsion. This turnover was regulated by CXCL12 which was induced by IFN-γ and acts to reduce turnover.

Gut contractility

This was another mechanism for expulsion of worms. This was shown to be under the control of Th2 cytokines within the gut that are produced during an effective immune response to an intestinal nematode. rIL-4L and STAT-6 were said to play a prominent role in muscle contractility and important mediator of resistance in Trichuris muris infection.

Intestinal permeability

By increasing amount of fluid in gut expulsion of worm's increases and limits access to surface epithelium IL13 and IL4 are able to change intestinal epithelial function to induce an influx of fluid into the gut lumen which helped in expulsion of Trichuris muris worms

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