Involvement of Toso in activation of monocytes, macrophages, and granulocytes

Karl S. Lang, Philipp A. Lang, Andreas Meryk, Aleksandra A. Pandyra, Louis Martin Boucher, Vitaly I. Pozdeev, Michael W. Tusche, Joachim R. Göthert, Jillian Haight, Andrew Wakeham, Annick J. You-Ten, David R. McIlwain, Katja Merches, Vishal Khairnar, Mike Recher, Garry P. Nolan, Yasumichi Hitoshi, Pauline Funkner, Alexander A. Navarini, Admar VerschoorNamir Shaabani, Nadine Honke, Linda Z. Penn, Pamela S. Ohashi, Dieter Häussinger, Kyeong Hee Lee, Tak W. Mak*

*Corresponding author for this work
38 Citations (Scopus)


Rapid activation of immune responses is necessary for antibacterial defense, but excessive immune activation can result in life-threatening septic shock. Understanding how these processes are balanced may provide novel therapeutic potential in treating inflammatory disease. Fc receptors are crucial for innate immune activation. However, the role of the putative Fc receptor for IgM, known as Toso/Faim3, has to this point been unclear. In this study, we generated Toso-deficient mice and used them to uncover a critical regulatory function of Toso in innate immune activation. Development of innate immune cells was intact in the absence of Toso, but Toso-deficient neutrophils exhibited more reactive oxygen species production and reduced phagocytosis of pathogens compared with controls. Cytokine production was also decreased in Toso -/- mice compared with WT animals, rendering them resistant to septic shock induced by lipopolysaccharide. However, Toso-/- mice also displayed limited cytokine production after infection with the bacterium Listeria monocytogenes that was correlated with elevated presence of Listeria throughout the body. Accordingly, Toso-/- mice succumbed to infections of L. monocytogenes, whereas WT mice successfully eliminated the infection. Taken together, our data reveal Toso to be a unique regulator of innate immune responses during bacterial infection and septic shock.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
Pages (from-to)2593-2598
Number of pages6
Publication statusPublished - 12.02.2013

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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