TY - JOUR
T1 - Transport of antibody into the skin is only partially dependent upon the neonatal Fc-receptor
AU - Nasir, Gibran
AU - Sinnis, Photini
N1 - Publisher Copyright:
Copyright: © 2023 Nasir, Sinnis. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2023/4
Y1 - 2023/4
N2 - The dermis is the portal of entry for most vector-transmitted pathogens, making the host's immune response at this site critical in mitigating the magnitude of infection. For malaria, antibody-mediated neutralization of Plasmodium parasites in the dermis was recently demonstrated. However, surprisingly little is known about the mechanisms that govern antibody transport into the skin. Since the neonatal Fc receptor (FcRn) has been shown to transcytose IgG into various tissues, we sought to understand its contribution to IgG transport into the skin and antibody-mediated inhibition of Plasmodium parasites following mosquito bite inoculation. Using confocal imaging, we show that the transport of an anti-Langerin mAb into the skin occurs but is only partially reduced in mice lacking FcRn. To understand the relevance of FcRn in the context of malaria infection, we use the rodent parasite Plasmodium berghei and show that passively-administered anti-malarial antibody in FcRn deficient mice, does not reduce parasite burden to the same extent as previously observed in wild-type mice. Overall, our data suggest that FcRn plays a role in the transport of IgG into the skin but is not the major driver of IgG transport into this tissue. These findings have implications for the rational design of antibody-based therapeutics for malaria as well as other vector-transmitted pathogens.
AB - The dermis is the portal of entry for most vector-transmitted pathogens, making the host's immune response at this site critical in mitigating the magnitude of infection. For malaria, antibody-mediated neutralization of Plasmodium parasites in the dermis was recently demonstrated. However, surprisingly little is known about the mechanisms that govern antibody transport into the skin. Since the neonatal Fc receptor (FcRn) has been shown to transcytose IgG into various tissues, we sought to understand its contribution to IgG transport into the skin and antibody-mediated inhibition of Plasmodium parasites following mosquito bite inoculation. Using confocal imaging, we show that the transport of an anti-Langerin mAb into the skin occurs but is only partially reduced in mice lacking FcRn. To understand the relevance of FcRn in the context of malaria infection, we use the rodent parasite Plasmodium berghei and show that passively-administered anti-malarial antibody in FcRn deficient mice, does not reduce parasite burden to the same extent as previously observed in wild-type mice. Overall, our data suggest that FcRn plays a role in the transport of IgG into the skin but is not the major driver of IgG transport into this tissue. These findings have implications for the rational design of antibody-based therapeutics for malaria as well as other vector-transmitted pathogens.
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U2 - 10.1371/journal.pone.0273960
DO - 10.1371/journal.pone.0273960
M3 - Article
C2 - 37093800
AN - SCOPUS:85153687047
SN - 1932-6203
VL - 18
JO - PloS one
JF - PloS one
IS - 4 4
M1 - e0273960
ER -