bims-inflim 2018-04-08 papers

Issue of 2018–04–08
three papers selected by
Christine Oshansky-Weilnau

Curr Opin Immunol. 2018 Mar 28. pii: S0952-7915(18)30012-8. [Epub ahead of print]53 1-6

Toward universal influenza virus vaccines: from natural infection to vaccination strategy.

Conceptually, a universal influenza vaccine should elicit broadly protective antibody responses targeting highly conserved epitope(s) shared by various virus strains. Strategically directing antibody immunity to the conserved hemagglutinin stalk has recently emerged as a promising approach that is substantiated by the identification of naturally occurring, stalk-reactive human antibodies capable of conferring broad protection against influenza virus challenge in animal models. Despite all the advancements, future realization of this strategy still faces many challenges, particularly whether it is able to induce enough of cross-reactive antibody response to protect against pandemic viruses. In this respect, recent in-depth dissections of human immune responses to H7N9 virus and vaccination provide much-needed new insights.

DOI: https://doi.org/10.1016/j.coi.2018.03.020

Curr Opin Virol. 2018 Mar 28. pii: S1879-6257(17)30162-1. [Epub ahead of print]29 62-71

The use of humanized mice for studies of viral pathogenesis and immunity.

Florian Douam, Alexander Ploss.

Humanized mice, that is, animals engrafted with human tissues and/or expressing human genes, have been instrumental in improving our understanding of the pathogenesis and immunological processes that define some of the most challenging human-tropic viruses. In particular, mice engrafted with components of a human immune system (HIS) offer unprecedented opportunities for mechanistic studies of human immune responses to infection. Here, we provide a brief overview of the current panel of HIS mouse models available and cite recent examples of how such humanized animals have been used to study immune responses and pathogenesis elicited by human-tropic viruses. Finally, we will outline some of the challenges that lay ahead and strategies to improve and refine humanized mice with the goal of more accurately recapitulating human immune responses to viral infection.

DOI: https://doi.org/10.1016/j.coviro.2018.03.003

Biol Chem. 2018 Mar 01. pii: /j/bchm.just-accepted/hsz-2018-0114/hsz-2018-0114.xml. [Epub ahead of print]

Woodys Lenga Ma Bonda, Sophie Iochmann, Mélia Magnen, Yves Courty, Pascale Reverdiau.

Human tissue kallikreins (KLKs) are 15 members of the serine protease family and are present in various healthy human tissues including airway tissues. Multiple studies have revealed their crucial role in the pathophysiology of a number of chronic, infectious and tumour lung diseases. KLK1, 3 and 14 are involved in asthma pathogenesis, and KLK1 could be also associated with the exacerbation of this inflammatory disease caused by rhinovirus. KLK5 was demonstrated as an influenza virus activating protease in humans, and KLK1 and 12 could also be involved in the activation and spread of these viruses. KLKs are associated with lung cancer, with up- or downregulation of expression depending on the KLK, cancer subtype, stage of tumour and also the microenvironment. Functional studies showed that KLK12 is a potent pro-angiogenic factor. Moreover, KLK6 promotes malignant-cell proliferation and KLK13 invasiveness. In contrast, KLK8 and KLK10 reduce proliferation and invasion of malignant cells. Considering the involvement of KLKs in various physiological and pathological processes, KLKs appear to be potential biomarkers and therapeutic targets for lung diseases.

Keywords: ECM remodelling; asthma; cancer; influenza; protease; respiratory tract

DOI: https://doi.org/10.1515/hsz-2018-0114