Intercellular communication in inflammatory response

Group Information

The group is interested in studying the interactions between pathogenic bacteria and cells from the immune system. It has recently discovered a new pathway for the capture of bacteria by T cells i.e. bacterial transinfection. Certain pathogenic bacteria (Listeria monocytogenes, Salmonella enterica and Shigella flexneri) are capable of invading T lymphocytes in vivo and modifying their behaviour.

The group has dissected the bacterial uptake pathway by cells; transinfection from previously infected dendritic cells (DCs). The transinfection process requires direct contact between the two cell types and is strongly increased by antigenic presentation. This new mechanism of bacterial capture by T cells is much more effective than direct capture and is directed by T cells. It is worth noting that some viruses e.g. HIV, use a similar transinfection mechanism to access CD4+ T lymphocytes through infected DCs.

Surprisingly, transinfected T cells killed captured bacteria in the first few hours after infection in a more efficient way than professional phagocytes such as DCs. Therefore, T cells, the paradigm of cells from the adaptive immune system, could perform functions that were previously thought to be exclusive to components of innate immunity; T lymphocytes can capture and destroy bacteria in a similar way to innate immunity. In addition, transinfected T cells (ti) secrete large amounts of pro-inflammatory cytokines (IL-6, interferon-γ and TNF-α), which play important roles in the elimination of bacteria and efficiently protect in vivo against the “challenge” with Listeria monocytogenes.

Lines of Research

Four main lines of research will be developed.

1.- We will study whether tiT cells act as bona fide antigen-presenting cells (data have been obtained showing that tiT cells are excellent cross presenters), and the molecular mechanisms that control the new functions of tiT cells.

2.- The possible use of these cells in cancer immunotherapy will be addressed due to their extraordinary cross presentation and hyper-inflammatory character. TiT cells could become promising new troops to join in the fight against cancer.

3.- Transinfection will be analysed as a mechanism of capture/destruction/presentation of bacterial antigens to B cells.

4.- Whether tiT lymphocytes could protect against bacterial infections will be explored as an alternative to antibiotics. This would be extremely relevant as anti-microbial resistance has become an increasingly serious threat to global public health according to the World Health Organization.

Team members

area-1-Linea-1-G2-Dr-Veiga-web

Group leader:

Esteban Veiga Chacón.

Universidad Autónoma de Madrid – Hospital Universitario de La Princesa.

  Other team members. Hospital Universitario Santa Cristina:

  • Aránzazu Cruz Adalia
  • Mónica Torres Torresano
Projects

Veiga Chacón, Esteban. Aplicaciones terapéuticas de linfocitos transinfectados; nuevos agentes en la inmunoterapia contra el cáncer. BFU2014-59585-R. MINECO. 2015-2017.

Veiga Chacón, Esteban. Red de excelencia para la explotación de bacterias con fines terapéuticos. SAF2014-56716-REDT. MINECO. 2014-2016.

Publications

Cruz-Adalia A, Ramirez-Santiago G, Calabia-Linares C, Torres-Torresano M, Feo L, Galán-Díez M, Fernández-Ruiz E, Pereiro E, Guttmann P, Chiappi M, Schneider G, Carrascosa JL, Chichón FJ, Martínez Del Hoyo G, Sánchez-Madrid F, Veiga E. T Cells Kill Bacteria Captured by Transinfection from Dendritic Cells and Confer Protection in Mice. Cell Host Microbe 2014. 15: 611-622. FI: 12.328(Q1). PMID: 24832455. DOI: 10.1016/j.chom.2014.04.006.

Morlino G, Barreiro O, Baixauli F, Robles-Valero J, González-Granado JM, Villa-Bellosta R, Cuenca J, Sánchez-Sorzano CO, Veiga E, Martín-Cófreces NB, Sánchez-Madrid F. Miro-1 Links Mitochondria and Microtubule Dynein Motors To Control Lymphocyte Migrati. PMID: 24492963. DOI: 10.1128/MCB.01177-13.

Calabia-Linares, Carmen, Robles-Valero, Javier, de la Fuente, Hortensia, Perez-Martinez, Manuel, Martin-Cofreces, Noa, Alfonso-Perez, Manuel, Gutierrez-Vazquez, Cristina, Mittelbrunn, Maria, Ibiza, Sales, Urbano-Olmos, Francisco R., Aguado-Ballano, Covadonga, Oscar Sanchez-Sorzano, Carlos, Sanchez-Madrid, Francisco, Veiga, Esteban. Endosomal clathrin drives actin accumulation at the immunological synapse. J Cell Sci 2011. 124: 820-830. FI: 6.111(Q1). PMID: 21321329. DOI: 10.1242/jcs.078832.

Baixauli, Francesc, Martin-Cofreces, Noa B., Morlino, Giulia, Carrasco, Yolanda R., Calabia-Linares, Carmen, Veiga, Esteban, Serrador, Juan M., Sanchez-Madrid, Francisco. The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse. EMBO J 2011. 30: 1238-1250. FI: 9.205(Q1). PMID: 21326213. DOI: 10.1038/emboj.2011.25.

Visvikis, Orane, Boyer, Laurent, Torrino, Stephanie, Doye, Anne, Lemonnier, Marc, Lores, Patrick, Rolando, Monica, Flatau, Gilles, Mettouchi, Amel, Bouvard, Daniel, Veiga, Esteban, Gacon, Gerard, Cossart, Pascale, Lemichez, Emmanuel. Escherichia coli Producing CNF1 Toxin Hijacks Tollip to Trigger Rac1-Dependent Cell Invasion. TRAFFIC 2011. 12: 579-590. FI: 4.919(Q2). P PMID: 21291504. DOI: 10.1111/j.1600-0854.2011.01174.x.