Monocytes from chronic HBV patients react in vitro to HBsAg and TLR by producing cytokines irrespective of stage of disease.
Individuals who are chronically infected with the hepatitis B virus (HBV) are highly heterogeneous with respect to serum levels of HBV DNA, HBV particles and viral proteins. Since circulating leukocytes, such as monocytes, are constantly exposed to these viral components, it is likely that the functionality of these cells is affected. However, at present, little information is available on the consequences of the interaction between monocytes and viral components. Therefore, we examined the in vitro effects of HBV surface antigen (HBsAg) on monocytes and evaluated whether these effects were reflected in vivo. We observed that in vitro HBsAg exposure of monocytes induced robust production of IL-6 and TNF. However, between chronic HBV patients with distinct levels of serum HBsAg, HBV early antigen (HBeAg), and HBV DNA, TLR-induced monocyte cytokine production did not differ. Importantly, HBsAg-induced cytokine production by monocytes was similar between patients and healthy controls showing that earlier in vivo exposure to HBsAg does not affect the in vitro response. Additionally, we show that IL-10 is able to inhibit cytokine production by HBsAg-induced monocytes. In conclusion, we demonstrate that monocytes can recognize and respond to HBsAg, resulting in vigorous pro-inflammatory cytokine production in vitro. However, phenotype and function of the monocyte compartment in chronic HBV patients are not influenced by differences in levels of serum viral components, suggesting that regulatory mechanisms are active to avoid excessive in vivo monocyte activation.
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Arjan
A
Boltjes
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Zwier M
ZM
Groothuismink
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Gertine W
GW
van Oord
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Liver Clinic University Health Network, Division of Gastroenterology, University of Toronto, Toronto, ON, Canada.
Harry L A
HL
Janssen
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Andrea M
AM
Woltman
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
André
A
Boonstra
D000293:Adolescent; D000328:Adult; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000276:immunology* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D055815:Young Adult
D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10