Macrophages and neutrophils are the first responders to invading pathogens and contribute strongly to the host defense against intracellular pathogens. The collective interplay and dynamic interactions between these leukocytes are to a large extent not understood. In the present study, we have investigated their role using a combination of confocal laser-scanning and electron microscopy in a zebrafish model for tuberculosis, a local Mycobacterium marinum infection in the tissue of the larval tail fin. Our results show that neutrophils are efficient in phagocytosis of mycobacteria and that they contribute largely to their dissemination. Macrophages appear to play a major role in efferocytosis, phagocytosis of dead cells that contain bacterial content. Phagocytic cells with large bacterial aggregates are formed that can be extruded out of the tissue after cell death. Alternatively, these excessively infected cells can undergo necrosis leading to immediate recruitment of surrounding leukocytes and subsequent phagocytosis of released bacteria. Our data show that these necrotic burst events result in progression of the infection, whereas extrusion abates the infection.
The authors declare no competing or financial interests.
Conceptualization, R.H., A.H.M., H.P.S. and M.J.M.S.; methodology, R.H. and G.E.M.L.; formal analysis, R.H.; investigation, R.H., G.E.M.L. and H.M.S.; writing original draft, R.H. and M.J.M.S.; writing, review and editing, M.J.M.S, A.H.M. and H.P.S.; supervision, M.J.M.S and H.P.S.; funding acquisition, H.P.S.
Infectious disease research in our laboratory is supported by the European Union Seventh Framework Programme project ZF-HEALTH [grant number HEALTH-F4-2010-242048] and the Cyttron II Program [LSH framework number FES0908].
The movies associated with this paper are deposited at dryad: http://dx.doi.org/10.5061/dryad.08803
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.135194.supplemental
- Received February 15, 2016.
- Accepted July 25, 2016.
- © 2016. Published by The Company of Biologists Ltd