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Immune response gene polymorphisms in tuberculosis

100%

Fol M., Druszczynska M., Wlodarczyk M., Ograczyk E., Rudnicka W.

issue 4

633-640

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (M.tb), remains a leading public health problem in most parts of the world. Despite the discovery of the bacilli over 100 years ago, there are still many unanswered questions about the host resistance to TB. Although one third of the world's population is infected with virulent M.tb, no more than 5-10% develop active disease within their lifetime. A lot of studies suggest that host genetic factors determine the outcome of M.tb-host interactions, however, specific genes and polymorphisms that govern the development of TB are not completely understood. Strong evidence exists for genes encoding pattern recognition receptors (TLR, CD14), C-type lectins, cytokines/chemokines and their receptors (IFN-γ, TNF-α, IL-12, IL-10, MCP-1, MMP-1), major histocompatibility complex (MHC) molecules, vitamin D receptor (VDR), and proton-coupled divalent metal ion transporters (SLC11A1). Polymorphisms in these genes have a diverse influence on the susceptibility to or protection against TB among particular families, ethnicities and races. In this paper, we review recent discoveries in genetic studies and correlate these findings with their influence on TB susceptibility.

The balance between pro- and anti-inflammatory cytokines in the immune responses to BCG and DTwP vaccines

73%

Druszczynska M., Kowalewicz-Kulbat M., Maszewska A., Rudnicka K., Szpakowski P., Wawrocki S., Wlodarczyk M., Rudnicka W.

issue 4

913-921

Bacillus Calmette-Guérin (BCG) and pertussis vaccines have been found to be insufficient and their further improvement is required. In order to develop improved vaccines, a better understanding of the main pathways involved in the host's protective immunity to the pathogens is crucial. We address the question as to whether the balance between pro- and anti-inflammatory cytokine production might affect the host responses to BCG and diphtheria-tetanus toxoids-whole cell pertussis (DTwP) vaccines. The study population consisted of 118 healthy people, age range 18-30 years, who had been subjected to BCG and DTwP vaccination according to the state policy. Tuberculin skin testing (TST) revealed a delayed type hypersensitivity (DTH) to PPD (purified protein derivative) in 53% volunteers. The variability in development of the BCG-driven DTH to tuberculin prompted us to address a question as to whether Th1/Th2 polarization is involved in the lack of skin responsiveness to PPD. PPD-stimulated blood lymphocytes from TST+ participants produced significantly more IFN-γ and less IL-10 than lymphocytes from TST- volunteers. However, TST- volunteers' sera contained more anti-pertussis IgG but not anti-diphtheria toxin IgG. Mycobacterial antigens and particularly PPD induced a higher expression of HLA-DR and co-stimulatory CD80 receptors on DCs from TST+ than TST- participants. BCG but not PPD pulsed DCs from TST- volunteers produced significantly more IL-10. Mycobacterial antigen stimulated DCs from TST+ volunteers induced a more intense IFN-γ production in co-cultures with autologous lymphocytes than the cells from TST- participants. Differences among the types of dendritic cell activities contribute to development of tuberculin reactivity in BCG vaccinated volunteers.

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2 Acta Biochimica Polonica

2 2015

2 Druszczynska M.

2 Rudnicka W.

2 Wlodarczyk M.

1 Fol M.

1 Kowalewicz-Kulbat M.

1 Maszewska A.

1 Ograczyk E.

1 Rudnicka K.

1 Szpakowski P.

1 Wawrocki S.

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Immune response gene polymorphisms in tuberculosis

The balance between pro- and anti-inflammatory cytokines in the immune responses to BCG and DTwP vaccines