Tissue damage control

Sepsis describes a common and often deadly medical syndrome. It is defined as a combination of an infection and associated with organ dysfunction. It is now widely accepted that the extent of tissue dysfunction and damage directly correlates with disease severity and outcome of the patients. The cellular and molecular mechanisms driving disease progression from a mild, non-critical infection to the development of multi-organ failure in sepsis are not understood. Recent evidence by others and us suggests that an inappropriate adaptation of the host parenchymal metabolism is a major determinant of tissue dysfunction underlying septic organ failure. The individual disease course of sepsis will depend on the intrinsic capacity of the host organism to maintain tissue homeostasis and integrity via a defense mechanism that is referred to as Disease Tolerance. Disease tolerance relies on mechanisms that reduce the negative impact on host fitness by conferring Tissue Damage Control.

The interest in this field is based on the observation with Miguel Soares at the Instituto Gulbenkian de Ciência that an appropriate metabolic adaptation depending on iron metabolism maintains glucose homeostasis promotes disease tolerance to bacterial infection. General mechanisms affording metabolic energetic adaptation and restoring metabolic homeostasis in parenchymal tissues however are largely unknown and are investigated by several group members using different approaches and in vitro as well as in vivo infectious disease models. The group is also running the first disease tolerance clinical trial (EPOS-1). For further information on this, please see Clinical Studies.

Five most important publications

Soares MP, Gozzelino R, Weis S (2014) Tissue damage control in disease tolerance. Trends Immunol 35(10), 483-94.

Weis S, Weis S, Carlos AR, Moita MR, Singh S, Blankenhaus B, Cardoso S, Larsen R, Rebelo S, Schäuble S, Del Barrio L, Mithieux G, Rajas F, Lindig S, Bauer M, Soares MP (2017) Metabolic adaptation establishes disease tolerance to sepsis. Cell 169(7), 1263-75 e14.

Weis S, Rubio I, Ludwig K, Weigel C, Jentho E (2017) Hormesis and Defense of Infectious Disease. Int J Mol Sci 18(6).

Vandewalle J, Timmermans S, Paakinaho V, Vancraeynest L, Dewyse L, Vanderhaeghen T, Wallaeys C, Van Wyngene L, Van Looveren K, Nuyttens L, Eggermont M, Dewaele S, Velho TR, Moita LF, Weis S, Sponholz C, van Grunsven LA, Dewerchin M, Carmeliet P, De Bosscher K, Van de Voorde J, Palvimo JJ, Libert C (2021) Combined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis. Cell Metab 33(9), 1763-76 e5.

Colaço HG, Barros A, Neves-Costa A, Seixas E, Pedroso D, Velho T, Willmann KL, Faisca P, Grabmann G, Yi HS, Shong M, Benes V, Weis S, Köcher T, Moita LF (2021) Tetracycline antibiotics induce host-dependent disease tolerance to infection. Immunity 54(1), 53-67 e7.


Max Schubert