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LAG-3 Role in Infection †

Oncoimmunology Unit, Navarrabiomed-Fundación Miguel Servet, Universidad Pública de Navarra (UPNA), Hospital Universitario de Navarra (HUN), Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Division of Gene Therapy and Regulation of Gene Expression, Cima Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdISNA), 31008 Pamplona, Spain
Medical Oncology Unit, Hospital Universitario de Navarra (HUN), Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Authors to whom correspondence should be addressed.
Presented at the 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases, online, 1–14 September 2021.
Med. Sci. Forum 2021, 7(1), 14;
Published: 31 August 2021


Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions [1,2,3]. LAG-3 negatively regulates proliferation, activation, effector function and homeostasis of both CD4 and CD8 T cells. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule, especially as a potential next-generation target for anti-cancer-targeted therapies. A systematic research was performed using the PubMed and databases. Articles published up to 2021 meeting the inclusion criteria were investigated. LAG-3 expression has been linked to increased pathology in certain infections, such as the ones caused by Salmonella, Plasmodium parasites, Mycobacterium tuberculosis, human immunodeficiency virus (HIV), non-pathogenic simian immunodeficiency virus (SIV), in hepatitis B virus (HBV), human papillomavirus (HPV), chronic hepatitis C virus (HCV), lymphocytic choriomeningitis virus (LCMV) and herpes simplex virus 1 (HSV-1) [4,5,6,7,8,9,10,11,12]. Its upregulation in infection is usually associated with a high viral and bacterial load and a reduced survival rate, correlating with faster disease progression and a suppression of viral-specific, T cell-mediated immunity [6,8,12]. LAG-3 inhibits cell proliferation, cytotoxicity function, and cytokine production in response to infection [13]. For example, LAG-3 expression is significantly upregulated in hepatitis B virus (HBV)-specific CD8 T cells, acting as a suppressor of HBV-specific, cell-mediated immunity or even to the pathogenesis of hepatocellular carcinoma [7,12], and it enhances high bacterial burdens together with changes in Th1 responses during active Mycobacterium tuberculosis infections, with an increased expression in the lungs and particularly within the granulomatous lesions [10]. It also correlates with a high viral load within T cell exhausted cells in HIV infection [6]. Here, we will discuss the impaired control of cell-mediated immunity associated with the high accumulation of LAG-3 after infection in most cases associated with a high bacterial/viral load, a reduced survival rate or persisting metabolic and inflammation disorders. Interestingly, the in vitro blockade of PD-1/LAG-3 interactions enhanced cytokine production in response to some of these infections.

Supplementary Materials

The following supporting information can be downloaded at:


This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.


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MDPI and ACS Style

Chocarro, L.; Blanco, E.; Arasanz, H.; Bocanegra, A.; Fernández-Rubio, L.; Echaide, M.; Garnica, M.; Ramos, P.; Kochan, G.; Escors, D. LAG-3 Role in Infection. Med. Sci. Forum 2021, 7, 14.

AMA Style

Chocarro L, Blanco E, Arasanz H, Bocanegra A, Fernández-Rubio L, Echaide M, Garnica M, Ramos P, Kochan G, Escors D. LAG-3 Role in Infection. Medical Sciences Forum. 2021; 7(1):14.

Chicago/Turabian Style

Chocarro, Luisa, Ester Blanco, Hugo Arasanz, Ana Bocanegra, Leticia Fernández-Rubio, Miriam Echaide, Maider Garnica, Pablo Ramos, Grazyna Kochan, and David Escors. 2021. "LAG-3 Role in Infection" Medical Sciences Forum 7, no. 1: 14.

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