The Neoehrlichia Eosinophil (NEOs) Project

The Neoehrlichia project

Neoehrlichia mikurensis is a strict intracellular bacterium that is carried by ticks and wild rodents and is widely spread in Europa and Asia. Human beings can become infected by this bacterium via tick-bites and develop the infectious disease “neoehrlichiosis”. Neoehrlichiosis typically presents as fever of uncertain cause in immunosuppressed patients, but the infection can also give rise to a skin rash or no symptoms at all. A striking feature of neoehrlichiosis is the high incidence of associated vascular complications that can afflict the venous as well as the arterial sides of the circulation.

The goals of our project are to elucidate the pathogenic mechanisms by which Neoehrlichia mikurensis infects cells, causes vascular complications, and persists in the human body, as well as the risk factors associated with severe disease and the features of protective immunity.

References

Welinder-Olsson C, Kjellin E, Vaht K, Jacobsson S, Wennerås C. First case of human “Candidatus Neoehrlichia mikurensis” infection in a febrile patient with chronic lymphocytic leukemia. J Clin Microbiol 48(5):1956-1959, 2010.

Granqvist A, P-O Andersson, Mattsson M, Sender M, Vaht K, Höper L, Sakiniene E, Stenson M, Trysberg E, Fehr J, Pekova S, Bogdan C, Bloemberg G, Wennerås C. Infections with the tick-borne bacterium “Candidatus Neoehrlichia mikurensis” mimic non-infectious conditions in patients with B cell malignancies or autoimmune diseases. Clin Infect Dis, 58(12):1716-1722, 2014.

Wass L, Grankvist A, Bell-Sakyi L, Bergström M, Ulfhammer E, Lingblom C, Wennerås C. Cultivation of the causative agent of neoehrlichiosis from clinical isolates identifies endothelium as a target of infection. Emerg Microb Infect, 8(1):413-425, 2019.

The Eosinophil project

Eosinophilic granulocytes are part of type 2 immune responses, together with Th2 lymphocytes and mast cells. We have shown that human eosinophils can regulate and suppress the function of T lymphocytes and have identified a population of suppressive eosinophils. Part of the T cell suppressive function of eosinophils is mediated via galectin-10, formerly known as the Charcot-Leyden crystal protein. The goals of our project are to unravel the molecular mechanisms by which eosinophils suppress excessive T cell proliferation and activation. This is done in the context of two inflammatory conditions driven by T cells with eosinophil involvement: the allergic disease eosinophilic esophagitis, and graft-versus-host disease, a complication that afflicts every other patient who has undergone allogeneic blood stem cell transplantation. Another aim of this project is to develop non-invasive diagnostic methods based on phenotypic analyses of blood eosinophils to diagnose these two diseases that currently rely on collection of biopsies from afflicted tissues.

References

Andersson* J, Cromvik* J, Ingelsten M, Andersson K, Johansson J-E, Wennerås C. Eosinophils from hematopoietic stem cell recipients suppress allogeneic T-cell proliferation. Biol Blood Marrow Transplant, 20(12):1891-1898, 2014.

Lingblom C, Wallander J, Ingelsten M, Bergquist H, Bove M, Saalman R, Welin A, Wennerås C. eosinophils from eosinophilic esophagitis patients have T cell suppressive capacity and express Foxp3. Clin Exp Immunol, 187(3):455-465, 2017.

Lingblom C, Andersson J, Andersson K, Wennerås C. Regulatory eosinophils suppress T cells partly through galectin-10. J Immunol, 198:4672-4681, 2017.