Intravital Microscopy in Infection and Immunity

Whether or not an infected organism is successful in defending itself against a pathogen depends primarily upon the interaction of the cells within the immune system – both among one another and with the pathogen. The “language” of these interactions, soluble and membrane-linked signal molecules, has been thoroughly examined in recent years. The manner in which these signals are exchanged within the living organism is still unclear. With the aid of specialized microscopy technologies, the interplay between host and pathogen can be tracked nowadays in living tissues.

Leader

Selected Publications

Philipsen L, Reddycherla AV, Hartig R, Gumz J, Kastle M, Kritikos A, Poltorak MP, Prokazov Y, Turbin E, Weber A, Zuschratter W, Schraven B, Simeoni L, Muller AJ (2017) De novo phosphorylation and conformational opening of the tyrosine kinase Lck act in concert to initiate T cell receptor signaling. Science signaling 10 

Olekhnovitch R, Ryffel B, Muller AJ#, Bousso P# (2014) Collective nitric oxide production provides tissue-wide immunity during Leishmania infectionJ Clin Invest 124: 1711-1722 #equally contributing corresponding authors 

Muller AJ#, Aeschlimann S, Olekhnovitch R, Dacher M, Spath GF, Bousso P# (2013) Photoconvertible Pathogen Labeling Reveals Nitric Oxide Control of Leishmania major Infection In Vivo via Dampening of Parasite Metabolism. Cell Host Microbe 14: 460-467 #equally contributing corresponding authors 

Muller AJ#, Filipe-Santos O, Eberl G, Aebischer T, Spath GF, Bousso P# (2012) CD4(+) T Cells Rely on a Cytokine Gradient to Control Intracellular Pathogens beyond Sites of Antigen Presentation. Immunity 37: 147-157 #equally contributing corresponding authors 

Muller AJ, Kaiser P, Dittmar KE, Weber TC, Haueter S, Endt K, Songhet P, Zellweger C, Kremer M, Fehling HJ, Hardt WD (2012) Salmonella gut invasion involves TTSS-2-dependent epithelial traversal, basolateral exit, and uptake by epithelium-sampling lamina propria phagocytes. Cell Host  Microbe 11: 19-32 

Publications

Glodde N, Bald T, Boorn-Konijnenberg D, Nakamura K, Szczepanski S, Brandes M, Eickhoff S, Shridhar N, Hinze D, Rogava M, van der Sluis T, Ruotsalainen J, Gaffal G, Landsberg J, Ludwig K, Wilhelm C, Riek-Burchardt M, Müller AJ, Gebhardt C, Janzen V, Kastenmüller W, Smyth M, Mazzone M, Tüting T, and Hölzel M. c-MET dependent reactive neutrophil responses limit immunotherapy of cancer Immunity in press 

van Ham M, Teich R, Philipsen L, Niemz J, Amsberg N, Wissing J, Nimtz M, Grobe L, Kliche S, Thiel N, Klawonn F, Hubo M, Jonuleit H, Reichardt P, Muller AJ, Huehn J, Jansch L (2017) TCR signalling network organization at the immunological synapses of murine regulatory T cells. Eur J Immunol. 2017 Aug 17. doi: 10.1002/eji.201747041. [Epub ahead of print]  

Madhusudhan T, Wang H, Ghosh S, Dong W, Kumar V, Al-Dabet MM, Manoharan J, Nazir S, Elwakiel A, Bock F, Kohli S, Marquardt A, Sogut I, Shahzad K, Muller AJ, Esmon CT, Nawroth PP, Reiser J, Chavakis T, Ruf W, Isermann B (2017) Signal integration at the PI3K-p85-XBP1 hub endows coagulation protease activated protein C with insulin like function. Blood 130:1445-1455 

Witte A, Meineke B, Sticht J, Philipsen L, Kuropka B, Muller AJ, Freund C, Schraven B, Kliche S (2017) D120 and K152 within the PH Domain of T Cell Adapter SKAP55 Regulate Plasma Membrane Targeting of SKAP55 and LFA-1 Affinity Modulation in Human T Lymphocytes. Molecular and cellular biology 37 

Philipsen L, Reddycherla AV, Hartig R, Gumz J, Kastle M, Kritikos A, Poltorak MP, Prokazov Y, Turbin E, Weber A, Zuschratter W, Schraven B, Simeoni L, Muller AJ (2017) De novo phosphorylation and conformational opening of the tyrosine kinase Lck act in concert to initiate T cell receptor signaling. Science signaling 10 

Volckmar J, Gereke M, Ebensen T, Riese P, Philipsen L, Lienenklaus S, Wohlleber D, Klopfleisch R, Stegemann-Koniszewski S, Muller AJ, Gruber AD, Knolle P, Guzman CA, Bruder D (2017) Targeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver. Scientific reports 7: 43985 

Hurrell BP, Beaumann M, Heyde S, Regli IB, Muller AJ, Tacchini-Cottier F (2017) Frontline Science: Leishmania mexicana amastigotes can replicate within neutrophils. J Leukoc Biol. pii: doi: 10.1189/jlb.4HI0417-158R. 

Mohle L, Israel N, Paarmann K, Krohn M, Pietkiewicz S, Muller A, Lavrik IN, Buguliskis JS, Schott BH, Schluter D, Gundelfinger ED, Montag D, Seifert U, Pahnke J, Dunay IR (2016) Chronic Toxoplasma gondii infection enhances beta-amyloid phagocytosis and clearance by recruited monocytes. Acta neuropathologica communications 4: 25 

Hurrell BP, Schuster S, Grun E, Coutaz M, Williams RA, Held W, Malissen B, Malissen M, Yousefi S, Simon HU, Muller AJ, Tacchini-Cottier F (2015) Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion. PLoS Pathog 11: e1004929 JIF=7.4

Olekhnovitch R, Ryffel B, Muller AJ#, Bousso P(2014) Collective nitric oxide production provides tissue-wide immunity during Leishmania infection. J Clin Invest 124: 1711-1722 #equally contributing corresponding authors 

Muller AJ#, Aeschlimann S, Olekhnovitch R, Dacher M, Spath GF, Bousso P# (2013) Photoconvertible Pathogen Labeling Reveals Nitric Oxide Control of Leishmania major Infection In Vivo via Dampening of Parasite Metabolism. Cell Host Microbe 14: 460-467 #equally contributing corresponding authors 

Felmy B, Songhet P, Slack EM, Muller AJ, Kremer M, Van Maele L, Cayet D, Heikenwalder M, Sirard JC, Hardt WD (2013) NADPH oxidase deficient mice develop colitis and bacteremia upon infection with normally avirulent, TTSS-1- and TTSS-2-deficient Salmonella Typhimurium. PLoS One 8: e77204 

Muller AJ#, Filipe-Santos O, Eberl G, Aebischer T, Spath GF, Bousso P# (2012) CD4(+) T Cells Rely on a Cytokine Gradient to Control Intracellular Pathogens beyond Sites of Antigen Presentation. Immunity 37: 147-157 #equally contributing corresponding authors 

Muller AJ, Kaiser P, Dittmar KE, Weber TC, Haueter S, Endt K, Songhet P, Zellweger C, Kremer M, Fehling HJ, Hardt WD (2012) Salmonella gut invasion involves TTSS-2-dependent epithelial traversal, basolateral exit, and uptake by epithelium-sampling lamina propria phagocytes. Cell Host  Microbe 11: 19-32 

Celli S, Day M, Muller AJ, Molina-Paris C, Lythe G, Bousso P (2012) How many dendritic cells are required to initiate a T-cell response? Blood 120: 3945-3948 

Songhet P, Barthel M, Stecher B, Muller AJ, Kremer M, Hansson GC, Hardt WD (2011) Stromal IFN-gammaR-signaling modulates goblet cell function during Salmonella Typhimurium infection. PLoS One 6: e22459 

Joller N, Weber SS, Muller AJ, Sporri R, Selchow P, Sander P, Hilbi H, Oxenius A (2010) Antibodies protect against intracellular bacteria by Fc receptor-mediated lysosomal targeting. Proc Natl Acad Sci U S A 107: 20441-20446 

Endt K, Stecher B, Chaffron S, Slack E, Tchitchek N, Benecke A, Van Maele L, Sirard JC, Mueller AJ, Heikenwalder M, Macpherson AJ, Strugnell R, von Mering C, Hardt WD (2010) The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea. PLoS Pathog 6: e1001097 

Lindemann A, Koch M, Pessi G, Muller AJ, Balsiger S, Hennecke H, Fischer HM (2010) Host-specific symbiotic requirement of BdeAB, a RegR-controlled RND-type efflux system in Bradyrhizobium japonicum. FEMS microbiology letters 312: 184-191 

Muller AJ, Hoffmann C, Hardt WD (2010) Caspase-1 activation via Rho GTPases: a common theme in mucosal infections? PLoS Pathog 6: e1000795 

Hoffmann C, Galle M, Dilling S, Kappeli R, Muller AJ, Songhet P, Beyaert R, Hardt WD (2010) In macrophages, caspase-1 activation by SopE and the type III secretion system-1 of S. typhimurium can proceed in the absence of flagellin. PLoS One 5: e12477 

Muller AJ, Hoffmann C, Galle M, Van Den Broeke A, Heikenwalder M, Falter L, Misselwitz B, Kremer M, Beyaert R, Hardt WD (2009) The S. Typhimurium effector SopE induces caspase-1 activation in stromal cells to initiate gut inflammation. Cell Host Microbe 6: 125-136 

Hapfelmeier S§Muller AJ§, Stecher B, Kaiser P, Barthel M, Endt K, Eberhard M, Robbiani R, Jacobi CA, Heikenwalder M, Kirschning C, Jung S, Stallmach T, Kremer M, Hardt WD (2008) Microbe sampling by mucosal dendritic cells is a discrete, MyD88-independent step in DeltainvG S. Typhimurium colitis. J Exp Med 205: 437-450 §equally contributing first authors 

Schlumberger MC, Kappeli R, Wetter M, Muller AJ, Misselwitz B, Dilling S, Kremer M, Hardt WD (2007) Two newly identified SipA domains (F1, F2) steer effector protein localization and contribute to Salmonella host cell manipulation. Mol Microbiol 65: 741-760 

Schlumberger MC, Muller AJ, Ehrbar K, Winnen B, Duss I, Stecher B, Hardt WD (2005) Real-time imaging of type III secretion: Salmonella SipA injection into host cells. Proc Natl Acad Sci U S A 102: 12548-12553 

Hapfelmeier S, Stecher B, Barthel M, Kremer M, Muller AJ, Heikenwalder M, Stallmach T, Hensel M, Pfeffer K, Akira S, Hardt WD (2005) The Salmonella pathogenicity island (SPI)-2 and SPI-1 type III secretion systems allow Salmonella serovar typhimurium to trigger colitis via MyD88-dependent and MyD88-independent mechanisms. J Immunol 174: 1675-1685 

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