Protective effects of recombinant human granulocyte macrophage colony stimulating factor on H1N1 influenza virus-induced pneumonia in mice

Huang, Hai; Li, Hong; Zhou, Pei; Ju, Dianwen

doi:10.1016/j.cyto.2010.04.001

Cited by 22 publications

(29 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GM-CSF enhances mucosal immune responses and the effectiveness of DNA vaccines (Herbert et al, 2009; Loudon et al, 2010). Direct administration of GM-CSF to the lung facilitates host resistance and survival from influenza infection (Huang et al, 2011, 2010). GM-CSF is expressed transiently 2 days after acute infection with influenza A in mice (Hennet et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

GM-CSF modulates pulmonary resistance to influenza A infection

et al. 2011

View full text Add to dashboard Cite

Alveolar type II epithelial or other pulmonary cells secrete GM-CSF that regulates surfactant catabolism and mucosal host defense through its capacity to modulate the maturation and activation of alveolar macrophages. GM-CSF enhances expression of scavenger receptors MARCO and SR-A. The alveolar macrophage SP-R210 receptor binds the surfactant collectin SP-A mediating clearance of respiratory pathogens. The current study determined the effects of epithelial-derived GM-CSF in host resistance to influenza A pneumonia. The results demonstrate that GM-CSF enhanced resistance to infection with 1.9 × 104 ffc of the mouse-adapted influenza A/Puerto Rico/8/34 (PR8) H1N1 strain, as indicated by significant differences in mortality and mean survival of GM-CSF-deficient (GM−/−) mice compared to GM−/− mice in which GM-CSF is expressed at increased levels. Protective effects of GM-CSF were observed both in mice with constitutive and inducible GM-CSF expression under the control of the pulmonary-specific SFTPC or SCGB1A1 promoters, respectively. Mice that continuously secrete high levels of GM-CSF developed desquamative interstitial pneumonia that impaired long-term recovery from influenza. Conditional expression of optimal GM-CSF levels at the time of infection, however, resulted in alveolar macrophage proliferation and focal lymphocytic inflammation of distal airways. GM-CSF enhanced alveolar macrophage activity as indicated by increased expression of SP-R210 and CD11c. Infection of mice lacking the GM-CSF-regulated SR-A and MARCO receptors revealed that MARCO decreases resistance to influenza in association with increased levels of SP-R210 in MARCO−/− alveolar macrophages. In conclusion, GM-CSF enhances early host resistance to influenza. Targeting of MARCO may reinforce GM-CSF-mediated host defense against pathogenic influenza.

show abstract

Section: Introductionmentioning

confidence: 99%

GM-CSF modulates pulmonary resistance to influenza A infection

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Numerous studies have shown that GM-CSF KO mice are more susceptible to a variety of pathogens in the lung 19,20). Furthermore, administration of recombinant human GM-CSF has a protective effect in mice infected with influenza A virus (25). To assess the contribution of engrafted human alveolar macrophages to lung host defense, we therefore infected engrafted h/h mice with influenza A/PR8 (H1N1) virus via the intranasal route and measured production of human cytokines.…”

Section: Homozygous Hil-3/gm-csf Ki Mice Mount Correlates Of a Humanmentioning

confidence: 99%

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung

Willinger¹,

Rongvaux²,

Takizawa

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

209

189

View full text Add to dashboard Cite

Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and function of human myeloid cells and the absence of human immune responses at mucosal surfaces, such as the lung. To overcome this, we generated human IL-3/GM-CSF knock-in (hIL-3/GM-CSF KI) mice. These mice faithfully expressed human GM-CSF and IL-3 and developed pulmonary alveolar proteinosis because of elimination of mouse GM-CSF. We demonstrate that hIL-3/GM-CSF KI mice engrafted with human CD34 + hematopoietic cells had improved human myeloid cell reconstitution in the lung. In particular, hIL-3/GM-CSF KI mice supported the development of human alveolar macrophages that partially rescued the pulmonary alveolar proteinosis syndrome. Moreover, human alveolar macrophages mounted correlates of a human innate immune response against influenza virus. The hIL-3/GM-CSF KI mice represent a unique mouse model that permits the study of human mucosal immune responses to lung pathogens.

show abstract

“…It is crucially involved in antimicrobial pulmonary host defense (19,20) and ameliorates lung injury when applied systemically to IV-infected mice (21) by increasing size and activation of the alveolar macrophage pool (22,23). Previously, 2 studies have demonstrated that GM-CSF drives the accumulation of CD11b + DC populations in the gut lamina propria under homeostatic conditions (24,25).…”

Section: Introductionmentioning

confidence: 99%