| First Author | Wüthrich M | Year | 2012 |
| Journal | Immunity | Volume | 36 |
| Issue | 4 | Pages | 680-92 |
| PubMed ID | 22483803 | Mgi Jnum | J:182207 |
| Mgi Id | MGI:5315015 | Doi | 10.1016/j.immuni.2012.02.015 |
| Citation | Wuthrich M, et al. (2012) Fungi subvert vaccine T cell priming at the respiratory mucosa by preventing chemokine-induced influx of inflammatory monocytes. Immunity 36(4):680-92 |
| abstractText | Vaccinologists strive to harness immunity at mucosal sites of pathogen entry. We studied respiratory delivery of an attenuated vaccine against Blastomyces dermatitidis. We created a T cell receptor transgenic mouse responsive to vaccine yeast and found that mucosal vaccination led to poor T cell activation in the draining nodes and differentiation in the lung. Mucosal vaccination subverted lung T cell priming by inducing matrix metalloproteinase 2 (MMP2), which impaired the action of the chemokine CCL7 on egress of CCR2(+) Ly6C(hi) inflammatory monocytes from the bone marrow and their recruitment to the lung. Studies in Mmp2(-/-) mice, or treatment with MMP inhibitor or rCCL7, restored recruitment of Ly6C(hi) monocytes to the lung and CD4(+) T cell priming. Mucosal vaccination against fungi and perhaps other respiratory pathogens may require manipulation of host MMPs in order to alter chemokine signals needed to recruit Ly6C(hi) monocytes and prime T cells at the respiratory mucosa. |
