Martin Rottenberg and Hans Wigzell Group
Welcome to the internet home of the Martin Rottenberg and Hans Wigzell group! Here you can find out about our research interests. We are located on level B3 of MTC, so you know if you want to come and say hello. If you want to know more than you can find on these pages you are welcome to contact us.
The intracellular Mycobacterium tuberculosis infects a large number of individuals. However, only a small fraction of the infected individuals will develop Tuberculosis. TB will reactivate in a fraction of asymptomatically infected individuals. It is not completely understood why some individuals will develop a life threatening disease while others harbour a lifelong asymptomatic infection, but cytokines with rapid induction and high local concentration are of importance. To avoid host cell damage, cytokine responses must be controlled.
Suppressor of cytokine signalling-3 (SOCS3) inhibit STAT3 activation in response to different cytokines. We employed mice knocked down of SOCS3 expression in different immune populations. Interestingly, mice lacking SOSC3 in either macrophages and neutrophils (by targeting the LysM gene) or in T cells (by targeting the lck gene) were both found to be extremely susceptible to M. tuberculosis infection.
While SOCS3 in myeloid (macrophages and dendritic cells) promoted protection by allowing a fast and potent release of IL-12, allowing IFN-Gamma secretion by Th1 cells, SOCS3 expression in T cells regulated the levels of Gamma Delta+ T cells, and was associated to increased IL-17 secretion and neutrophil accumulation. SOCS3 thus regulates different biological responses in diverse immune cell populations that independently play a critical role in defense against the infection.
We have used humanized mice, in which human immune cells differentiate de novo from transplanted cord blood progenitor cells, to study the human immune responses to infection with Mycobacterium bovis BCG and M. tuberculosis.
Granulomas mainly composed of human macrophages surrounded by T cells resembling those of human Tuberculosis, were observed in organs from infected mice. The lesions from mice depleted of CD4+ T cells were scarcer, minimal and irregular compared to those from mice depleted of CD8+ cells or non-depleted controls.
Granulomas of BCG-infected humanized mice administered with a TNF-neutralizing TNF receptor fusion molecule preserved their structure, but contained higher levels of intracellular bacilli. Thus, humanized mice can be used as a model to study the formation and maintenance of human granuloma in TB and other infectious or non- infectious diseases.
The penetration of T cells and trypanosomes into the brain parenchyma is a major pathogenetic event in African trypanosomiasis, caused by infection of the protozoan parasite Trypanosoma brucei. The role of innate immune responses in the penetration of T cells and Trypanosoma brucei into the brain was studied in different knockout mice. Our data indicate that parasite stimulate innate immune TLR signals induce the expression of TNF-alpha and IFN-alpha/beta. These cytokines are required for invasion of T cells and trypanosomes into the brain. TLR signal also control T.b. brucei load in the brain by molecules distinct from TNF and IFN-alpha/beta.
Project Groups with the Martin Rottenberg Group
Spatial and temporal localization of immune transcripts defines hallmarks and diversity in the tuberculosis granuloma. Berit Carow, Thomas Hauling, Xiaoyan Qian, Igor Kramnik, Mats Nilsson & Martin E. Rottenberg. Nature Communicationsvolume 10, Article number: 1823 (2019)
|Annelie Brauner||Professor, senior|
|Berit Annika Carow||Senior lab manager|
|Rakesh Kumar Majhi||Postdoc|
Former group members
Genetically controlled interactions between mycobacteria and host cells that are regulated by the host innate and adaptive immune responses dictate the outcome of mycobacterial infection.