Cytokine transcripts in pediatric tuberculosis: a study with bronchoalveolar cells
E M Aubert-Pivert1, F M Chedevergne, G M Lopez-Ramirez
1Unité de Génétique Mycobactérienne, Département de Physiopathologie, Institut Pasteur, 25 rue du Docteur Roux, 75728 Paris Cedex 15, France. epivert@pasteur.fr
Insights
Pediatric tuberculosis (TB) involves distinct cytokine profiles. This study found elevated immunosuppressive cytokines, transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10), in children with TB, suggesting reduced Th1 responses.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- Respiratory Medicine
Background:
- Pediatric tuberculosis (TB) presents differently than adult TB.
- Cytokine expression in pediatric TB remains understudied.
- Cytokines at the infection site influence TB disease progression and pathology.
Purpose of the Study:
- To investigate cytokine transcript expression in bronchoalveolar cells (BACs) from children with TB.
- To compare cytokine profiles between pediatric TB patients and those with other pulmonary diseases.
- To understand the role of cytokines in pediatric TB pathogenesis.
Main Methods:
- Collected bronchoalveolar cells (BACs) from 9 children with TB and 9 with other pulmonary diseases.
- Developed an RT-PCR method to quantify mRNA for six key cytokines: IFN-γ, IL-12, TNF-α, IL-10, IL-4, and TGF-β1.
- Analyzed and compared cytokine mRNA expression levels between the two groups.
Main Results:
- Children with TB showed significantly higher TGF-β, TNF-α, and IFN-γ mRNA in BACs compared to controls.
- TGF-β mRNA levels were high, while IFN-γ and TNF-α mRNA levels were low in TB patients.
- Elevated IL-10 transcripts were observed in miliary TB, and TGF-β in non-miliary TB, indicating overproduction of immunosuppressive cytokines.
Conclusions:
- Overproduction of immunosuppressive cytokines TGF-β and IL-10 is implicated in pediatric TB progression.
- The findings suggest a reduction in Th1 immune responses in children suffering from TB.
- Cytokine profiling provides insights into the unique immunological aspects of pediatric tuberculosis.
Abstract:
Pediatric tuberculosis (TB) differs from adult TB in many features. To date, cytokine expression has not been studied in children with TB. The relative amounts of the various cytokines released at the site of infection may be important determinants of TB disease development and pathology. We determined cytokine transcripts in bronchoalveolar cells (BACs) recovered from 9 children presenting with TB and from 9 children with pulmonary diseases other than TB. An RT-PCR-based method was developed to quantify the mRNAs encoding six cytokines (IFN- gamma, IL-12, TNF- alpha, IL-10, IL-4, TGF- beta 1) known to play key roles in mycobacterial infections. Expression of mRNA encoding TGF- beta, TNF- alpha and IFN- gamma was statistically significantly higher in BACs from children with TB than in BACs from children with other pulmonary diseases; whereas the levels of mRNA transcription for TGF- beta is high, the levels of mRNA transcription for IFN- gamma and TNF- alpha remain low. All children had low levels of mRNA for IL-12(p40). IL-4 was barely detectable in all cases. Children with miliary TB had high levels of IL-10 transcripts and low levels of mRNA encoding TGF- beta. The immunosuppressive cytokines TGF- beta and IL-10, are overproduced in children with non-miliary TB and miliary TB respectively and are probably involved in the progression of the disease. These data suggest that Th1 responses are reduced in children with TB.
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