TLR2 and TLR4 expression on CD14(++) and CD14(+) monocyte subtypes in adult-onset autoimmune diabetes.
BACKGROUND
Peripheral blood monocytes are key effectors of innate immunity. Dysfunction, changes in their counts or altered expression of cytokines and pattern-recognition receptors on monocytes may contribute to the development of the autoimmune type of diabetes mellitus (AD).


OBJECTIVE
We aimed to analyze the counts and proportions of the two main subtypes of monocyte cells, CD14(++) and CD14(+), and to look for potential changes in the expression of toll-like receptors 2 (TLR2) and 4 (TLR4) as well as cytokine prolactin (PRL) in adult-onset AD, including diabetes mellitus type 1 (T1DM) and latent autoimmune diabetes in adults (LADA).


METHODS
We examined 21 T1DM patients, 9 patients with LADA, 16 control patients with type 2 diabetes mellitus (T2DM) and 24 healthy individuals. All diabetic patients were diagnosed after the age of 18 years. Expression at the mRNA level was determined by quantitative PCR. Flow cytometry was used to ascertain membrane expression and cell counts.


RESULTS
T1DM patients had fewer CD14(++) (P < 0.01) and CD14(+) (P < 0.0001) monocytes whereas T2DM subjects showed decreased counts of CD14(+) monocytes compared to healthy controls (P < 0.001). TLR2 protein expression was significantly increased in T1DM CD14(+) monocytes compared to healthy controls (P < 0.05), while TLR4 expression in T1DM CD14(++) cells was significantly lower (P < 0.0001). There was no significant difference between the groups in terms of PRL mRNA expression in monocytes.


CONCLUSIONS
The observed changes in the proportions of both immune cell types and in the expression of functional pattern-recognition receptors on monocytes in the subjects examined may arise as a consequence of chronic inflammation that accompanies long-term diabetes.
Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Czech Republic.|Department of General Biology and Genetics, Third Faculty of Medicine, Charles University in Prague, Czech Republic.
Pavlina
P
Cejkova
Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Czech Republic.
Iva
I
Nemeckova
2nd Department of Internal Medicine, Diabetes Center, Third Faculty of Medicine, Charles University in Prague, Czech Republic.
Jan
J
Broz
Department of General Biology and Genetics, Third Faculty of Medicine, Charles University in Prague, Czech Republic.
Marie
M
Cerna
D000328:Adult; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
CD14 monocyte; adult-onset autoimmune diabetes; inflammation; prolactin; toll-like receptor