Yonsei Med J.  2013 May;54(3):707-714. 10.3349/ymj.2013.54.3.707.

Kinetics of IFN-Gamma and TNF-Alpha Gene Expression and Their Relationship with Disease Progression after Infection with Mycobacterium Tuberculosis in Guinea Pigs

• Roh IS
• Cho S
• Eum SY
• Cho SN

• KMID: 1727887
• DOI: http://doi.org/10.3349/ymj.2013.54.3.707

Abstract

PURPOSE
Guinea pig is one of the most suitable animal models for Mycobacterium tuberculosis (M. tb) infection since it shows similarities to pulmonary infection in humans. Although guinea pig shows hematogenous spread of M. tb infection into the whole body, immunological studies have mainly focused on granulomatous tissues in lungs and spleens. In order to investigate the time-course of disease pathogenesis and immunological profiles in each infected organ, we performed the following approaches with guinea pigs experimentally infected with M. tb over a 22-week post-infection period.
MATERIALS AND METHODS
We examined body weight changes, M. tb growth curve, cytokine gene expression (IFN-gamma and TNF-alpha), and histopathology in liver, spleen, lungs and lymph nodes of infected guinea pigs.
RESULTS
The body weights of infected guinea pigs did not increase as much as uninfected ones and the number of M. tb bacilli in their organs increased except bronchotracheal lymph node during the experimental period. The gene expression of IFN-gamma and TNF-alpha was induced between 3 and 6 weeks of infection; however, kinetic profiles of cytokine gene expression showed heterogeneity among organs over the study period. Histophathologically granulomatous lesions were developed in all four organs of infected guinea pigs.
CONCLUSION
Although IFN-gamma and TNF-alpha gene expression profiles showed heterogeneity, the granuloma formation was clearly observed in every organ regardless of whether the number of bacilli increased or decreased. However, this protective immunity was accompanied with severe tissue damage in all four organs, which may lead to the death of guinea pigs.

Keyword

Mycobacterium tuberculosis; pathogenesis; guinea pigs; IFN-gamma and TNF-alpha

MeSH Terms

Animals
Body Weight
*Disease Progression
Female
Gene Expression
Gene Expression Regulation
Guinea Pigs
Interferon-gamma/genetics/*metabolism
Kinetics
Liver/metabolism/pathology
Lung/metabolism/pathology
Lymph Nodes/metabolism/pathology
Mycobacterium tuberculosis
Spleen/metabolism/pathology
Tuberculosis/*genetics/pathology
Tumor Necrosis Factor-alpha/genetics/*metabolism
Tumor Necrosis Factor-alpha
Interferon-gamma