Genetic variability and immunological control of Anaplasma phagocytophilum (von Loewenich Laboratory)

Current Research

Genetic variability of Anaplasma phagocytophilum

Anaplasma phagocytophilum is an obligat intracellular bacterium that replicates in neutrophil granulocytes and causes febrile disease in humans and animals. In Europe, it is transmitted by Ixodes ricinus ticks. It In contrast to North America, human granulocytic anaplasmosis is a rare disease in Europe. Further, cross-infection experiments showed that A. phagocytophilum isolates of distinct host origin are not uniformly infectious for heterologous hosts. This led to several approaches of genetic characterization of A. phagocytophilum strains looking for molecular markers that could be associated with geographic origin or host species.

Since a variety of target genes was used previously, we developed a standardized multilocus sequence typing (MLST) scheme for A. phagocytophilum (http://pubmlst.org/). We could show that all strains from humans, dogs and horses belonged to the same clonal complex. Since granulocytic anaplasmosis in these animals is often diagnosed in Europe, most human cases might not be recognized. We currently characterize further strains by means of MLST and try to sequence whole genomes.

Immunological control of Anaplasma phagocytophilum

Since A. phagocytophilum replicates in a main cell of the innate immune system, it is used as model organism to study the immunological control of obligat intracellular pathogens. We showed using the mouse model that the control in the early phase of infection is IFNγ-dependent. In contrast, CD4⁺ T-cells are indispensable for bacterial elimination. To date, the effector mechanisms used by CD4⁺ T-cells are unclear because mice with defects for Th1 cytokines, perforin and Fas/Fas ligand were fully able to clear the infection. Therefore, we are studying in vitro whether a direct interaction between CD4⁺ T-cells and A. phagocytophilum infected granulocytes inhibits bacterial replication. For this purpose we use in vitro generated murine neutrophil granulocytes. Further, we use granulocytes defective for MHC I and MHC II to analyze whether antigen presentation by neutrophils is need for CD4⁺ T-cell dependent control. Respective genedeficient cell lines are used to study whether neutrophils itself contribute to the defense against A. phagocytophilum.

Members

Publications

2021

Müller BJ, Westheider A, Birkner K, Seelig B, Kirschnek S, Bogdan C, von Loewenich FD (2021) Anaplasma phagocytophilum induces TLR- and MyD88-dependent signaling in in vitro generated murine neutrophils. Frontiers in Cellular and Infection Microbiology. 11:627630. doi: 10.3389/fcimb.2021.627630

2020

Langenwalder DB, Schmidt S, Silaghi C, Skuballa J, Pantchev N, Matei IA, Mihalca AD, Gilli U, Zajkowska
J, Ganter M, Hoffman T, Salaneck E, Petrovec M, von Loewenich FD (2020) The absence of the drhm gene is not a marker for human-pathogenicity in European Anaplasma phagocytophilum strains. Parasites and Vectors. 13(1).

Langenwalder DB, Silaghi C, Nieder M, Pfeffer M, von Loewenich FD (2020) Co-infection, reinfection and superinfection with Anaplasma phagocytophilum strains in a cattle herd based on ankA gene and multilocus sequence typing. Parasites and Vectors. 2020; 13(1).

Mukhacheva TA, Shaikhova DR, Kovalev SY, von Loewenich FD (2020) Phylogeographical diversity of Anaplasma phagocytophilum in the Asian part of Russia based on multilocus sequence typing and analysis of the ankA gene. Infection Genetics and Evolution. 2020; 80.

von Loewenich FD, Seckert C, Dauber E, Kik MJL, de Vries A, Sprong H, Buschmann K, Aardema ML, Brandstetter M (2020) Prosthetic valve endocarditis with Bartonella washoensis in a human European patient and its detection in red squirrels (Sciurus vulgaris). Journal of Clinical Microbiology. 2020; 58(1).

2019

Langenwalder DB, Schmidt S, Gilli U, Pantchev N, Ganter M, Silaghi C, Aardema ML, von Loewenich FD (2019) Genetic characterization of Anaplasma phagocytophilum strains from goats (Capra aegagrus hircus) and water buffalo (Bubalus bubalis) by 16S rRNA gene, ankA gene and multilocus sequence typing. Ticks and Tick-Borne Diseases. 2019; 10(6).

Tegtmeyer P, Ganter M, von Loewenich FD (2019) Simultaneous infection of cattle with different Anaplasma phagocytophilum variants. Ticks and Tick-Borne Diseases. 2019; 10(5):1051-1056.

2018

Beger B, von Loewenich F, Goetze E, Moergel M, Walter C (2018) Leech related Aeromonas veronii complex infection after reconstruction with a microvascular forearm flap. J Maxillofac Oral Surg 17:68-70.

Kerz T, von Loewenich FD, Roberts J, Neulen A, Ringel F  (2018) Cerebrospinal fluid penetration of very high-dose meropenem: a case report. Ann Clin Microbiol Antimicrob 17:47

Weiss E, Hanzelmann D, Fehlhaber B, Klos A, von Loewenich FD, Liese J, Peschel A, Kretschmer D (2018) Formyl-peptide receptor 2 governs leukocyte influx in local Staphylococcus aureus infections. FASEB J 32:26-36.

2017

Gussmann K, Kirschnek S, von Loewenich FD (2017) Interferongamma-dependent control of Anaplasma phagocytophilum by murine neutrophil granulocytes. Parasit Vectors 10:329.

Silaghi C, Santos AS, Gomes J, Christova I, Matei IA, Walder G, Domingos A, Bell-Sakyi L, Sprong H, von Loewenich FD, Oteo JA, de la Fuente J, Dumler JS (2017) Guidelines for the Direct Detection of Anaplasma spp. in Diagnosis and Epidemiological Studies. Vector Borne Zoonotic Dis 17:12-22.

2016

Kerz T, Beyer C, Mole D, Oswald S, Frauenknecht K, von Loewenich FD, Schwanz T (2016) [Abscess-forming fungal encephalitis due to C. bantiana in an immunosuppressed patient]. Nervenarzt 87:191-194.

2015

Aardema ML, von Loewenich FD (2015) Varying influences of selection and demography in host-adapted populations of the ticktransmitted bacterium, Anaplasma phagocytophilum. BMC Evol Biol 15:58.

Strasek Smrdel K, von Loewenich FD, Petrovec M, Avsic Zupanc T (2015) Diversity of ankA and msp4 genes of Anaplasma phagocytophilum in Slovenia. Ticks Tick Borne Dis 6:164-166.

Wardecki T, Brotz E, De Ford C, von Loewenich FD, Rebets Y, Tokovenko B, Luzhetskyy A, Merfort I (2015) Endophytic Streptomyces in the traditional medicinal plant Arnica montana L.: secondary metabolites and biological activity. Antonie Van Leeuwenhoek 108:391-402.

2014

Gussmann K, Czech C, Hermann M, Schaarschmidt-Kiener D, von Loewenich FD (2014) Anaplasma phagocytophilum infection in a horse from Switzerland with severe neurological symptoms. Schweiz Arch Tierheilkd 156:345-348.

Hartwig V, von Loewenich FD, Schulze C, Straubinger RK, Daugschies A, Dyachenko V (2014) Detection of Anaplasma phagocytophilum in red foxes (Vulpes vulpes) and raccoon dogs (Nyctereutes procyonoides) from Brandenburg, Germany. Ticks Tick Borne Dis 5:277-280.

Huhn C, Winter C, Wolfsperger T, Wuppenhorst N, Strasek Smrdel K, Skuballa J, Pfaffle M, Petney T, Silaghi C, Dyachenko V, Pantchev N, Straubinger RK, Schaarschmidt-Kiener D, Ganter M, Aardema ML, von Loewenich FD (2014) Analysis of the population structure of Anaplasma phagocytophilum using multilocus sequence typing. PLoS One 9:e93725.

Schwab L, Goroncy L, Palaniyandi S, Gautam S, Triantafyllopoulou A, Mocsai A, Reichardt W, Karlsson FJ, Radhakrishnan SV, Hanke K, Schmitt-Graeff A, Freudenberg M, von Loewenich FD, Wolf P, Leonhardt F, Baxan N, Pfeifer D, Schmah O, Schonle A, Martin SF, Mertelsmann R, Duyster J, Finke J, Prinz M, Henneke P, Hacker H, Hildebrandt GC, Hacker G, Zeiser R (2014) Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med 20:648-654.