Role of CEACAM1 in antiviral immune responses
Virology
Final Report Abstract
The object of the project was to determine the role of CEACAM1 during virus infection. To do so we use CEACAM1 deficient mice, CEACAM1 transgenic mice, and CEACAM1 activating antibodies during infection with the lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus (VSV). In addition, we analyzed the role of CEACAM1 on human virus-specific CD8+ T cells in in vitro experiments. Identifying the most important mechanisms, how CEACAM1 influences immune cells was another goal. We found that CEACAM1 was important for maintaining the splenic architecture. Lack of CEACAM1 reduced the amount of CD169+ macrophages, limited enforced viral replication and resulted in reduced innate immune activation after infection with VSV. Furthermore, we found that B cell intrinsic expression of CEACAM1 was essential for survival of proliferating B cells. Therefore, lack of CEACAM1 in B cells limited antiviral B cell responses during VSV infection. During infection with LCMV, CEACAM1 was upregulated in CD8+ T cells. Lack of CEACAM1 on CD8+ T cells limited T cell expansion and resulted in virus persistence and higher immunopathology. Notably, activation of CEACAM1 by an anti-CEACAM1 antibody could restore CD8+ T cell function, led to fast virus clearance and lower immunopathology. Treatment of human virus-specific CD8+ T cells similarly enhanced CD8+ T cell function, which might make CEACAM1 a useful tool to modulate CD8+ T cell responses. Further evaluation has to be done to validate the role of CEACAM1 in human immune response and elucidate potential therapeutic applications.
Publications
- CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production. Nat Commun. 2015 Feb 18;6:6217
Khairnar V, Duhan V, Maney SK, Honke N, Shaabani N, Pandyra AA, Seifert M, Pozdeev V, Xu HC, Sharma P, Baldin F, Marquardsen F, Merches K, Lang E, Kirschning C, Westendorf AM, Häussinger D,Lang F, Dittmer U, Küppers R, Recher M, Hardt C, Scheffrahn I, Beauchemin N, Göthert JR, Singer BB, Lang PA, Lang KS
(See online at https://doi.org/10.1038/ncomms7217) - Carcinoembryonic antigen-related cell adhesion molecule 1 controls IL-2-dependent regulatory T-cell induction in immune-mediated hepatitis in mice. Hepatology. 2018 Jul;68(1):200- 214
Horst AK, Wegscheid C, Schaefers C, Schiller B, Neumann K, Lunemann S, Langeneckert AE, Oldhafer KJ, Weiler- Normann C, Lang KS, Singer BB, Altfeld M, Diehl L, Tiegs G
(See online at https://doi.org/10.1002/hep.29812) - CEACAM1 promotes CD8+ T cell responses and improves control of a chronic viral infection. Nat Commun. 2018 Jul 2;9(1):2561
Khairnar V, Duhan V, Patil AM, Zhou F, Bhat H, Thoens C, Sharma P, Adomati T, Friendrich SK, Bezgovsek J, Dreesen JD, Wennemuth G, Westendorf AM, Zelinskyy G, Dittmer U, Hardt C, Timm J, Göthert JR, Lang PA, Singer BB, Lang KS
(See online at https://doi.org/10.1038/s41467-018-04832-2) - Immunostimulatory anti-CEACAM1 antibody, US 10,106,608 B2, Oct. 23, 2018
Lang et al.
- CEACAM1 regulates CD8+ T cell immunity and protects from severe pathology during Citrobacter rodentium induced colitis. Gut Microbes. 2020 Jun 10:1-16
Zöller J, Ebel JF, Khairnar V, Schmitt V, Klopfleisch R, Meiners J, Seiffart V, Hansen W, Buer J, Singer BB, Lang KS, Westendorf AM
(See online at https://doi.org/10.1080/19490976.2020.1775464)
