Heterozygous Carriage of a Dysfunctional Toll-like Receptor 9 Allele Affects CpG Oligonucleotide Responses in B Cells

Knežević, Jelena; Pavlinić, Dinko; Rose, William Ii; Leifer, Cynthia A.; Bendelja, Krešo; Gabrilovac, Jelka; Parčina, Marijo; Lauc, Gordan; Kubarenko, Andriy V.; Petričević, Branka; Vrbanec, Damir; Bulat-Kardum, Ljiljana; Bekeredjian‐Ding, Isabelle; Pavelić, Jasminka; Dembić, Zlatko; Weber, Alexander N.R.

doi:10.1074/jbc.m111.337477

Cited by 5 publications

(1 citation statement)

References 44 publications

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“…DNA was isolated from blood samples of PTB patients (N=244) and contact controls (n=85) treated at the Section of Pulmology, Department of Internal Medicine, Clinical Hospital Centre Rijeka, Rijeka and Hospital for Lung Diseases “Jordanovac”, University Hospital Center “Zagreb”, and healthy blood donors (n=924) collected at Departments of Transfusion Medicine in Rijeka and in Zagreb, Croatia, as previously described36,37. DNA samples from the blood of additional 194 PTB patients, treated in Hospital for Lung Disease “Jordanovac”, University Hospital Center “Zagreb”, Croatia, were isolated at deCODE, Reykjavik, Iceland.…”

Section: Methodsmentioning

confidence: 99%

HLA class II sequence variants influence tuberculosis risk in populations of European ancestry

et al. 2016

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Mycobacterium tuberculosis (M. tuberculosis) infections cause 9.0 million new tuberculosis (TB) cases and 1.5 million deaths annually1. To search for sequence variants that confer risk of TB we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with TB (8,162 cases and 277,643 controls), pulmonary TB (PTB), and M. tuberculosis infection. We found association of three sequence variants in the HLA class II region: rs557011[T] (MAF=40.2%) with M. tuberculosis infection (OR =1.14, P=3.1×10-13) and PTB (OR=1.25, P=5.8×10-12) and rs9271378[G] (MAF=32.5%) with PTB (OR=0.78, P=2.5×10-12), both located between HLA-DQA1 and HLA-DRB1. Finally, a missense variant p.Ala210Thr in HLA-DQA1, (MAF=19.1%, rs9272785) shows association with M. tuberculosis infection (P=9.3×10-9, OR=1.14). The association of these variants with PTB was replicated in large samples of European ancestry from Russia and Croatia (P< 5.9×10-4). These findings demonstrate that the HLA class II region contributes to the complex genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells.

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Section: Methodsmentioning

confidence: 99%

HLA class II sequence variants influence tuberculosis risk in populations of European ancestry

et al. 2016

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Toll-like receptors and B cells: functions and mechanisms

Buchta

Bishop

2014

Immunol Res

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Numerous reports have described Toll-like receptor (TLR) functions in myeloid cells such as dendritic cells (DCs) and macrophages, but relatively fewer studies have examined TLR responses in B lymphocytes. B cells express a wide variety of TLRs and are highly activated after TLR ligation, leading to enhancements in B cell survival, surface molecule expression, cytokine and antibody production, and antigen presentation. During an immune response, B cells can receive signals through TLRs as well as the B cell antigen receptor (BCR) and/or CD40. TLR ligation synergizes with signals through these receptors and augments both innate and adaptive immune functions of B lymphocytes. Additionally, targeting B cell TLRs may provide new therapies against certain types of cancer as well as autoimmune diseases. Here, we summarize TLR expression and contributions to both normal and pathogenic functions in mouse and human B cells.

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TLR9 expressed on plasma membrane acts as a negative regulator of human B cell response

Guerrier

Pochard

Youinou

et al. 2014

Journal of Autoimmunity

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Heterozygous Carriage of a Dysfunctional Toll-like Receptor 9 Allele Affects CpG Oligonucleotide Responses in B Cells

Cited by 5 publications

References 44 publications

HLA class II sequence variants influence tuberculosis risk in populations of European ancestry

HLA class II sequence variants influence tuberculosis risk in populations of European ancestry

Toll-like receptors and B cells: functions and mechanisms

TLR9 expressed on plasma membrane acts as a negative regulator of human B cell response

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