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Reduced type I interferon production by dendritic cells and weakened antiviral immunity in patients with Wiskott-Aldrich syndrome protein deficiency.

Lang PA, Shaabani N, Borkens S, Honke N, Scheu S, Booth S, Brenner D, Meryk A, Barthuber C, Recher M, Mak TW, Ohashi PS, Häussinger D, Griffiths GM, Thrasher AJ, Bouma G, Lang KS - J. Allergy Clin. Immunol. (2012)

Bottom Line: Despite a significant proportion of patients with WAS having recurrent viral infections, surprisingly little is known about the effects of WASP deficiency on antiviral immunity.IFN-I production by WAS KO DCs was reduced both in vivo and in vitro.These findings might help us to understand the immunodeficiency of WAS.

View Article: PubMed Central - PubMed

Affiliation: Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ontario, Canada.

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Related in: MedlinePlus

Absence of WASP enhances virus-induced immunopathology. Virus-induced immunopathology was analyzed as serum alanine aminotransferase (ALT) activity (A) and bilirubin levels (B) after LCMV infection. Viral clearance was assessed by measuring viral titers in the liver (C). The presence of CD4+ and CD8+ T cells in the liver was analyzed by means of immunohistochemistry (D). Data in Fig 1, A and B, are means ± SEMs and peaks (Fig 1, A: C57BL/6 mice, n = 6-12; WAS KO mice, n = 8-10) or areas under the curve (Fig 1, B: C57BL/6 mice, n = 5-9; WAS KO mice, n = 5-6) compared by using the Student t test. Symbols in Fig 1, C, represent individual mice, and images in Fig 1, D, are representative of data shown in Fig 1, C.
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fig1: Absence of WASP enhances virus-induced immunopathology. Virus-induced immunopathology was analyzed as serum alanine aminotransferase (ALT) activity (A) and bilirubin levels (B) after LCMV infection. Viral clearance was assessed by measuring viral titers in the liver (C). The presence of CD4+ and CD8+ T cells in the liver was analyzed by means of immunohistochemistry (D). Data in Fig 1, A and B, are means ± SEMs and peaks (Fig 1, A: C57BL/6 mice, n = 6-12; WAS KO mice, n = 8-10) or areas under the curve (Fig 1, B: C57BL/6 mice, n = 5-9; WAS KO mice, n = 5-6) compared by using the Student t test. Symbols in Fig 1, C, represent individual mice, and images in Fig 1, D, are representative of data shown in Fig 1, C.

Mentions: To investigate the ability of WAS KO mice to mount a protective immune response against viral infection and to investigate immunopathology, we challenged mice with LCMV (WE strain). Serum alanine aminotransferase and total bilirubin levels were used as a direct measurement of virus-induced hepatic immunopathology.33 WAS KO mice showed a similar, although slightly earlier, alanine aminotransferase response but exhibited increased bilirubin levels after viral challenge (Fig 1, A and B). Furthermore, WAS KO mice showed persistence of viral replication and a hepatic T-cell infiltrate 15 days after infection, whereas by that time, wild-type C57BL/6 animals had cleared viral infection and showed no sign of T-cell infiltration (Fig 1, C and D). These finding indicate that WAS KO mice are compromised in their ability to clear LCMV, despite the presence of an inflammatory T-cell infiltrate.


Reduced type I interferon production by dendritic cells and weakened antiviral immunity in patients with Wiskott-Aldrich syndrome protein deficiency.

Lang PA, Shaabani N, Borkens S, Honke N, Scheu S, Booth S, Brenner D, Meryk A, Barthuber C, Recher M, Mak TW, Ohashi PS, Häussinger D, Griffiths GM, Thrasher AJ, Bouma G, Lang KS - J. Allergy Clin. Immunol. (2012)

Absence of WASP enhances virus-induced immunopathology. Virus-induced immunopathology was analyzed as serum alanine aminotransferase (ALT) activity (A) and bilirubin levels (B) after LCMV infection. Viral clearance was assessed by measuring viral titers in the liver (C). The presence of CD4+ and CD8+ T cells in the liver was analyzed by means of immunohistochemistry (D). Data in Fig 1, A and B, are means ± SEMs and peaks (Fig 1, A: C57BL/6 mice, n = 6-12; WAS KO mice, n = 8-10) or areas under the curve (Fig 1, B: C57BL/6 mice, n = 5-9; WAS KO mice, n = 5-6) compared by using the Student t test. Symbols in Fig 1, C, represent individual mice, and images in Fig 1, D, are representative of data shown in Fig 1, C.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3757164&req=5

fig1: Absence of WASP enhances virus-induced immunopathology. Virus-induced immunopathology was analyzed as serum alanine aminotransferase (ALT) activity (A) and bilirubin levels (B) after LCMV infection. Viral clearance was assessed by measuring viral titers in the liver (C). The presence of CD4+ and CD8+ T cells in the liver was analyzed by means of immunohistochemistry (D). Data in Fig 1, A and B, are means ± SEMs and peaks (Fig 1, A: C57BL/6 mice, n = 6-12; WAS KO mice, n = 8-10) or areas under the curve (Fig 1, B: C57BL/6 mice, n = 5-9; WAS KO mice, n = 5-6) compared by using the Student t test. Symbols in Fig 1, C, represent individual mice, and images in Fig 1, D, are representative of data shown in Fig 1, C.
Mentions: To investigate the ability of WAS KO mice to mount a protective immune response against viral infection and to investigate immunopathology, we challenged mice with LCMV (WE strain). Serum alanine aminotransferase and total bilirubin levels were used as a direct measurement of virus-induced hepatic immunopathology.33 WAS KO mice showed a similar, although slightly earlier, alanine aminotransferase response but exhibited increased bilirubin levels after viral challenge (Fig 1, A and B). Furthermore, WAS KO mice showed persistence of viral replication and a hepatic T-cell infiltrate 15 days after infection, whereas by that time, wild-type C57BL/6 animals had cleared viral infection and showed no sign of T-cell infiltration (Fig 1, C and D). These finding indicate that WAS KO mice are compromised in their ability to clear LCMV, despite the presence of an inflammatory T-cell infiltrate.

Bottom Line: Despite a significant proportion of patients with WAS having recurrent viral infections, surprisingly little is known about the effects of WASP deficiency on antiviral immunity.IFN-I production by WAS KO DCs was reduced both in vivo and in vitro.These findings might help us to understand the immunodeficiency of WAS.

View Article: PubMed Central - PubMed

Affiliation: Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ontario, Canada.

Show MeSH
Related in: MedlinePlus