Abstract
Pneumocystis is an important opportunistic fungus that causes pneumonia in children and immunocompromised individuals. Recent genomic data show that divergence of major surface glycoproteins may confer speciation and host range selectivity. On the other hand, immune clearance between mice and humans is well correlated. Thus, we hypothesized that humanize mice may provide information about human immune responses involved in controlling Pneumocystis infection. CD34-engrafted huNOG-EXL mice controlled fungal burdens to a greater extent than nonengrafted mice. Moreover, engrafted mice generated fungal-specific IgM. Fungal control was associated with a transcriptional signature that was enriched for genes associated with nonopsonic recognition of trophs (CD209) and asci (CLEC7A). These same genes were downregulated in CD4-deficient mice as well as twins with bare lymphocyte syndrome with Pneumocystis pneumonia.
Highlights
Animal models of Pneumocystis pneumonia (PCP) have been used for the discovery of new antimicrobial agents [1, 2] and vaccine testing [3, 4] as well as understanding CD4+ T cell immunity in the lung [5,6,7]
Recent genomic evidence shows that the major surface glycoproteins are the most divergent across species, and, surface interactions and attachment to host cells may play a key role in limitations of host range
This is similar to nonculturable components of the gut microbiota, where segmented filamentous bacteria (SFB) from rats will not infect mice unless the strain is complemented with the attachment proteins from murine SFB [8]
Summary
Animal models of Pneumocystis pneumonia (PCP) have been used for the discovery of new antimicrobial agents [1, 2] and vaccine testing [3, 4] as well as understanding CD4+ T cell immunity in the lung [5,6,7]. Recent genomic evidence shows that the major surface glycoproteins are the most divergent across species, and, surface interactions and attachment to host cells may play a key role in limitations of host range. This is similar to nonculturable components of the gut microbiota, where segmented filamentous bacteria (SFB) from rats will not infect mice unless the strain is complemented with the attachment proteins from murine SFB [8]. Without attachment to the epithelium, rat SFB fail to elicit T cell responses in the gastrointestinal tract [8]
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