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2011 ; 108
(6
): 2390-5
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Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and
human immune responses in the lung
#MMPMID21262803
Willinger T
; Rongvaux A
; Takizawa H
; Yancopoulos GD
; Valenzuela DM
; Murphy AJ
; Auerbach W
; Eynon EE
; Stevens S
; Manz MG
; Flavell RA
Proc Natl Acad Sci U S A
2011[Feb]; 108
(6
): 2390-5
PMID21262803
show ga
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.
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