Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia

Li, Liang1,2; Foo, Benjamin Jie Wei2; Kwok, Ka Wai2; Sakamoto, Noriho3; Mukae, Hiroshi3; Izumikawa, Koichi3; Mandard, Stephane4,5,6; Quenot, Jean-Pierre4,6,7,8; Lagrost, Laurent4,5,6,7; Teh, Wooi Keong9; Kohli, Gurjeet Singh10; Zhu, Pengcheng2; Choi, Hyungwon11; Buist, Martin Lindsay12; Seet, Ju Ee13; Yang, Liang2,10,14; He, Fang15,16; Chow, Vincent Tak Kwong17; Tan, Nguan Soon2,18

2019-05-01

10.1128/mBio.02469-18

mBio   影响因子和分区

2150-7511

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, anti-cANGPTL4 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.

ANGPTL4 secondary bacterial pneumonia antibiotic resistance host-directed immunotherapeutics vascular permeability

SCI

英语

其他

Mutant Mouse Regional Resource Center (MMRRC), an NIH[032147-UCD)]

Microbiology

Microbiology

WOS:000473596500080

AMER SOC MICROBIOLOGY

Web of Science

1.Chinese Acad Sci, Shenzhen Inst Adv Technol, Inst Biomed & Biotechnol, Shenzhen, Peoples R China
2.Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore
3.Nagasaki Univ, Unit Translat Med, Dept Resp Med, Grad Sch Biomed Sci, Nagasaki, Japan
4.INSERM, LNC, UMR1231, Dijon, France
5.Univ Bourgogne Franche Comte, LNC, UMR1231, Dijon, France
6.Fdn Cooperat Sci Bourgogne Franche Comte, LipSTIC LabEx, Dijon, France
7.Univ Hosp Dijon, Dijon, France
8.Univ Hosp Dijon, Intens Care Unit, Dijon, France
9.Nanyang Technol Univ, Interdisciplinary Grad Sch, SCELSE, Singapore, Singapore
10.Nanyang Technol Univ, SCELSE, Singapore, Singapore
11.Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore
12.Natl Univ Singapore, Dept Biomed Engn, Fac Engn, Singapore, Singapore
13.Natl Univ Singapore Hosp, Dept Pathol, Singapore, Singapore
14.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China
15.Zhejiang Univ, Coll Anim Sci, Inst Prevent Vet Med, Hangzhou, Zhejiang, Peoples R China
16.Zhejiang Univ, Coll Anim Sci, Zhejiang Prov Key Lab Prevent Vet Med, Hangzhou, Zhejiang, Peoples R China
17.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol & Immunol, Host & Pathogen Interact Lab, Singapore, Singapore
18.Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore

Li, Liang,Foo, Benjamin Jie Wei,Kwok, Ka Wai,et al. Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia[J]. mBio,2019,10(3).

Li, Liang.,Foo, Benjamin Jie Wei.,Kwok, Ka Wai.,Sakamoto, Noriho.,Mukae, Hiroshi.,...&Tan, Nguan Soon.(2019).Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia.mBio,10(3).

Li, Liang,et al."Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia".mBio 10.3(2019).