Head of the working group: Prof. Dr. Michael Neumaier

Immunorecognition is the central prime function for the detection of microbial and viral pathogens and for the discrimination of “self” and “non-self” as the very initial step of defending the organism or ensure its integrity.

A phylogenetically old “innate immune system” capable of recognizing pathogenic and damage-related molecular patterns (PAMPs and DAMPs, respectively) for self defense already exists in primitive invertebrate organisms.  Its pattern recognition receptors are highly effective, yet genome-encoded and thus invariant. With the evolution of higher vertebrates a very sophisticated “adaptive immune system” has developed capable of generating highly specific immune recognition receptors on demand.  Specifically, lymphoid cells recombine - through somatic genetic recombination - genetic building blocks to generate vast repertoires of variable immunoreceptors that can distinguish antigens at very high resolution.

While the two immune systems closely cooperate at the level of their biological effector functions, the ruling paradigm is that the “innate” and the “cognate” immune systems do not share their respective immunoreceptors, i.e. that there is no crosstalk between their immunorecognition functions.

We have first described a novel line of innate immune cells designated “Variable Immunoreceptor-expressing Myeloids” (VIREM) that are capable of genetically recombining and express variable immune receptors (antibodies and T-cell receptors), a clear break with a 100-year-old paradigm. Most recently, we have developed immune microscopy methods allowing the visualization of antibody-expressing VIREM (B-VIREM) Using state-of-the-art methods such as proteome analysis, NGS and single cell sequencing, FACS sorting and multi-omics. Recently, we have successfully characterized the first functional antibodies from B-VIREM-derived monoclonal antibodies. Currently, we are investigating the abundance and dynamic behavior of VIREM cells in the blood of patients with different health conditions and try to elucidate VIREM biological functions in our dedicated conditional KO mouse model and in cell culture models.

Dr. Volker Ast
PD Dr. Tina Fuchs
Dr. Maren Hedtke
Bettina Hill
Cornelia Keup
Dr. Jessica Krzistetzko
Prof. Dr. Michael Neumaier
Dr. Stefanie Nittka
Mathis Römer
Marina Talamini
Vanni Torresi

Mi3: MANNHEIM INSTITUTE for INNATE IMMUNOSCIENCE

Neumaier M, Giesler S, Ast V, Roemer M, Voß TD, Reinz E, Costina V, Schmelz M, Nürnberg E, Nittka S, Leppä AM, Rudolf R, Trumpp A, Fuchs T. Opsonization-independent antigen-specific recognition by myeloid phagocytes expressing monoclonal antibodies. Sci Adv. 2023 Sep;9(35):eadg1812. PMID: 37656789

Fuchs T*, Puellmann K*, Wang C, Han J, Beham AW, Neumaier M, Kaminski WE. Trilineage Sequencing Reveals Complex TCRβ Transcriptomes in Neutrophils and Monocytes Alongside T Cells. Genom Proteom Bioinform 2021; S1672-0229: 00044-9. PMID: 33662627

Fuchs T*, Hahn M*, Ries L, Giesler S, Busch S, Wang C, Han J, Schulze TJ, Puellmann K, Beham AW, Kaminski WE, Neumaier M. Expression of combinatorial immunoglobulins in macrophages in the tumor microenvironment. PLoS ONE. 2018 Sep 21; 13(9): e0204108. PMID: 30240437

Fuchs T*, ResPuellmann K*, Emmert A, Fleig J, Oniga S, Laird R, Heida NM, Schäfer K, Neumaier M, Beham AW, Kaminski WE. The macrophage-TCRαβ is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis. Biochem Biophys  Commun. 2015 Jan 2;456(1):59-65. PMID: 25446098

Beham AW*, Puellmann K*, Laird R*, Fuchs T*, Streich R, Breysach C, Raddatz D, Oniga S, Peccerella T, Findeisen P, Kzhyshkowska J, Gratchev A, Schweyer S, Saunders B, Wessels JT, Möbius W, Keane J, Becker H, Ganser A, Neumaier M, Kaminski WE.A TNF-regulated recombinatorial macrophage immune receptor implicated in granuloma formation in tuberculosis, PLoS Pathog. 2011 Nov;7(11):e1002375. PMID: 22114556

Further Reading: Pubmed