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Distinct response kinetics of gamma interferon and interleukin-4 in bovine tuberculosis
S G Rhodes1, N Palmer, S P Graham
1TB Research Group, Veterinary Laboratories Agency, Addlestone, Surrey KT15 3NB, United Kingdom. srhodes.vla@gtnet.gov.uk
Insights
Bovine tuberculosis involves gamma interferon (IFN-gamma) and interleukin-4 (IL-4) cytokine responses. Both cytokines help differentiate infected cattle, with IL-4 showing a delayed but significant response in M. bovis infections.
Area of Science:
- Veterinary Immunology
- Infectious Diseases
- Bovine Tuberculosis Research
Background:
- Mycobacterium bovis infection in cattle causes significant economic losses globally.
- Understanding host immune responses is crucial for diagnosing and controlling bovine tuberculosis.
- Gamma interferon (IFN-gamma) and interleukin-4 (IL-4) are key cytokines involved in cell-mediated immunity.
Purpose of the Study:
- To characterize the kinetics of IFN-gamma and IL-4 responses in cattle experimentally infected with M. bovis.
- To investigate the role of IL-4 in M. bovis infection, particularly in sub-clinical or early stages.
- To compare M. bovis-induced cytokine responses with those in naturally infected cattle and parasitic infections.
Main Methods:
- Experimental intratracheal infection of cattle with M. bovis.
- Measurement of IFN-gamma and IL-4 responses to bovine tuberculin and ESAT-6.
- Assessment of cytokine profiles in naturally infected cattle (field reactors).
- Comparison of IL-4 responses with those induced by Onchocerca ochengi infection.
Main Results:
- Early and sustained IFN-gamma response observed post-infection.
- Delayed and transient IL-4 response peaking at 6-8 weeks.
- Strong IL-4 responses detected even in cattle without clinical signs or strong IFN-gamma responses after a lower M. bovis challenge.
- Both IFN-gamma and IL-4 responses were elevated in naturally infected cattle and could differentiate infected from uninfected animals.
- Magnitude of M. bovis-induced IL-4 similar to that seen in parasitic nematode infections.
Conclusions:
- Both IFN-gamma and IL-4 are produced by peripheral blood cells in M. bovis-infected cattle.
- IL-4 plays a significant role in the immune response to M. bovis, even in the absence of overt disease.
- Cytokine profiling, including both IFN-gamma and IL-4, is valuable for diagnosing bovine tuberculosis in cattle.
Abstract:
This study shows that gamma interferon (IFN-gamma) and interleukin-4 (IL-4) cytokine responses are produced by peripheral blood cells in cattle infected with Mycobacterium bovis. The different kinetics of the IFN-gamma and IL-4 responses to bovine tuberculin and to ESAT-6 following experimental intratracheal infection with M. bovis are described. An early increase in IFN-gamma was observed that was maintained throughout the period studied. In contrast, the IL-4 response was delayed and confined to a peak of activity lasting 6 to 8 weeks. Interestingly, an experimental challenge of cattle with a lower dose of M. bovis which did not result in the development of lesions, positive DTH skin test, or substantial IFN-gamma responses nevertheless generated strong specific IL-4 responses. Investigation of naturally infected M. bovis field reactors showed increased IFN-gamma and IL-4 responses compared to uninfected cattle and that both of these cytokines were equally able to differentiate infected from uninfected animals. The magnitude of the M. bovis-induced IL-4 responses were found to be similar to the antigen-specific IL-4 responses of cattle infected with the parasitic nematode Onchocerca ochengi, further supporting the presence of this type 2 cytokine in bovine tuberculosis.