Patricia Barral, PhD
Lecturer in Immunobiology
Our research aims to understand the cellular and molecular mechanisms that underlie the initiation of immunity and how those contribute to human health and disease. We specifically focus on immune responses to lipids (both endogenous and from microbes) exploring how the immune system handles lipids, which are the mechanisms that mediate lipid recognition by immune cells and which are the consequences for human health when these processes are dysregulated.
Immune cells constantly patrol the body to recognize and destroy invading pathogens and consequently protect us from disease. The initiation of immune responses is the result of a complex process of activation of immune cells that critically depends on communication among different cell types and normally requires direct cell-cell interactions. A precise regulation of the location and interactions of immune cells are crucial to control their activation and consequently to preserve the balance between health and disease. Our studies seek to define how, where and when activation signals are delivered to immune cells and how these correlate with the initiation and outcome of immune responses.
Our research centers on immune responses to lipids. The immune system recognizes and responds to a variety of lipids such as those present on the cell wall from pathogenic bacteria (Streptococcus pneumoniae; Helicobacter pylori; Mycobacterium tuberculosis), fungi (Aspergillus fumigatus) or commensals. Immune responses to lipids are mediated by a unique population of cells (called NKT cells), which can specifically recognize lipids through their T cell receptors. Upon activation, NKT cells rapidly secrete large amounts of cytokines and induce downstream activation of different cell types, including B cells, NK cells, dendritic cells and macrophages. Consequently NKT cells play an important role on a variety of immune responses, including microbial infections, autoimmune diseases, allergy and tumor immunity. By combining in vivo models, imaging and genetics, we aim to uncover the features, distribution and dynamics of NKT cells within different tissues. We seek to understand how these parameters are altered during infectious and inflammatory processes and how NKT cell’s interactions with different lipid-presenting cells affect their activation, the activation of other immune cells and finally the outcome of immune responses.
- Barral P*, Sanchez-Niño MD, van Rooijen N, Cerundolo V, Batista FD*. The location of splenic NKT cells favors their rapid activation by blood-borne antigen. EMBO J 31:2378-2390 (2012) *Shared corresponding author.
- ChangPP, BarralP, FitchJ, MaCS, PratamaA, KalliesA, HoganJ, CerundoloV, TangyeSG, BittmanR, NuttSL, BrinkR, GodfreyDI, BatistaFD, VinuesaCG. Identification of Bcl-6-dependent NKT follicular helper cells that provide cognate help for B cell responses. Nat Immunol 13:35-43(2012)
- Barral P, Polzella P, Bruckbauer A, van Rooijen N, Besra GS, Cerundolo V, Batista FD. CD169+ macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes. Nat Immunol11:303-312 (2010)
- Barral P, Eckl-Dorna J, Harwood NE, De Santo C, Salio M, Illarionov P, Besra GS, Cerundolo V, Batista FD. B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo. PNAS USA 105:8345-8350 (2008)
- Saez de Guinoa J, Jimeno R, Farhadi N, Jervis PJ, Cox LR, Besra GS, Barral P. CD1d-mediated activation of group 3 innate lymphoid cells drives IL-22 production. EMBO Rep. 18:39-47 (2017)