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Title: Antibody treatment against angiopoietin-like 4 reduces pulmonary edema and injury in secondary pneumococcal pneumonia
Authors: Li, Liang
Foo, Benjamin Jie Wei
Kwok, Ka Wai
Sakamoto, Noriho
Mukae, Hiroshi
Izumikawa, Koichi
Mandard, Stéphane
Quenot, Jean-Pierre
Lagrost, Laurent
Teh, Wooi Keong
Zhu, Pengcheng
Choi, Hyungwon
Buist, Martin Lindsay
Seet, Ju Ee
Yang, Liang
He, Fang
Tan, Nguan Soon
Kohli, Gurjeet Singh
Chow, Vincent Tak Kwong
Keywords: Secondary Bacterial Pneumonia
Science::Biological sciences
Issue Date: 2019
Source: Li, L., Foo, B. J. W., Kwok, K. W., Sakamoto, N., Mukae, H., Izumikawa, K., . . . Tan, N. S. (2019). Antibody treatment against angiopoietin-like 4 reduces pulmonary edema and injury in secondary pneumococcal pneumonia. mBio, 10(3), e02469-18-. doi:10.1128/mBio.02469-18
Series/Report no.: mBio
Abstract: Secondary bacterial lung infection by Streptococcus pneumoniae (S.pneumoniae) poses a serious health concern, especially in developing countries. We posit that the emergence of multiantibiotic-resistant strains will jeopardize current treatments in these regions. Deaths arising from secondary infections are more often associated with acute lung injury, a common consequence of hypercytokinemia, than with the infection per se. Given that secondary bacterial pneumonia often has a poor prognosis, newer approaches to improve treatment outcomes are urgently needed to reduce the high levels of morbidity and mortality. Using a sequential dual-infection mouse model of secondary bacterial lung infection, we show that host-directed therapy via immunoneutralization of the angiopoietin-like 4 c-isoform (cANGPTL4) reduced pulmonary edema and damage in infected mice. RNA sequencing analysis revealed that anti-cANGPTL4 treatment improved immune and coagulation functions and reduced internal bleeding and edema. Importantly, anticANGPTL4 antibody, when used concurrently with either conventional antibiotics or antipneumolysin antibody, prolonged the median survival of mice compared to monotherapy. Anti-cANGPTL4 treatment enhanced immune cell phagocytosis of bacteria while restricting excessive inflammation. This modification of immune responses improved the disease outcomes of secondary pneumococcal pneumonia. Taken together, our study emphasizes that host-directed therapeutic strategies are viable adjuncts to standard antimicrobial treatments.
ISSN: 2161-2129
DOI: 10.1128/mBio.02469-18
Rights: © 2019 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:IGS Journal Articles
LKCMedicine Journal Articles
SBS Journal Articles
SCELSE Journal Articles


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