Modulation of cellular and humoral immune response to third party antigens in nematode-infected mice

• Applicant: Professorin Dr. Minka Breloer
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Immunology
• Term: from 2012 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 225759336

• Final Report Year: 2020

Final Report Abstract

Helminth parasites infect more than a quarter of the human population and inflict significant changes to the immunological status of their hosts. Analysing the impact of helminth infections on the efficacy of vaccinations we showed that concurrent infection with the parasitic nematode Litomosoides sigmodontis reduced the quantity and quality of antibody responses to vaccination against seasonal influenza in BALB/c and C57BL/6 mice. Vaccination-induced protection against challenge infections with the human pathogenic 2009 pandemic H1N1 influenza A virus was drastically impaired in helminth-infected mice. Impaired responses were also observed if vaccinations were performed after clearance of a previous helminth infection. This suggests that individuals in helminth-endemic areas may not always benefit from vaccinations, even in the absence of an acute and diagnosable helminth infection. Mechanistically the suppression is associated with a systemic and sustained expansion of IL-10-producing CD4+CD49+LAG-3+ type 1 regulatory T cells and partially abrogated by in vivo blockade of the IL-10 receptor. Consenting with these findings, concurrent L. sigmodontis infection interfered with the control of a retroviral infection by dampening the virus-specific neutralising Ab response.

Publications

• Filariae-retrovirus co-infection in mice is associated with suppressed virus-specific IgG immune response and higher viral loads. PLoS Neglected Tropical Diseases 2016; 10(12): e0005170
  Dietze KK, Dittmer U, Koudaimi DK, Schimmer S, Reitz M, Breloer M and Hartmann W
  
• Mucosal mast cells are indispensable for timely termination of Strongyloides ratti infection. Mucosal Immunology 2017; 10: 481-492
  Reitz M, Brunn ML, Rodewald HR, Feyerabend TB, Roers A, Dudeck A, Voeringer D, Jönsson F, Kühl AA and Breloer M
  
• Strongyloides infection in rodents: immune response and immune regulation: Parasitology 2017; 144: 295-315
  Breloer M and Abraham D
  
• Helminth infections suppress the efficacy of vaccination against seasonal influenza. Cell Reports 2019. 29, 2243-2256
  Hartmann W, Brunn M-L, Stetter N, Gagliani N, Muskate F, Stanelle-Bertram S, Gabriel G, and Breloer M