TY - JOUR
T1 - Zoonotic Visceral Leishmaniasis
T2 - New Insights on Innate Immune Response by Blood Macrophages and Liver Kupffer Cells to Leishmania infantum Parasites
AU - Rodrigues, Armanda Viana
AU - Valério-Bolas, Ana
AU - Alexandre-Pires, Graça
AU - Pereira, Maria Aires
AU - Nunes, Telmo
AU - Ligeiro, Dário
AU - da Fonseca, Isabel Pereira
AU - Santos-Gomes, Gabriela
N1 - Funding Information:
Funding: This study was supported by FCT-Foundation for Science and Technology, I.P., through research grant PTDC/CVT-CVT/28908/2017 and PTDC/CVT-CVT/0228/2020, and by national funds within the scope of Centro de Investigação Interdisciplinar em Sanidade Animal (CIISA, UIDB/00276/2020) and Global Health and Tropical Medicine (GHTM, UID/04413/2020).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1
Y1 - 2022/1
N2 - L. infantum is the aetiological agent of zoonotic visceral leishmaniasis (ZVL), a disease that affects humans and dogs. Leishmania parasites are well adapted to aggressive conditions inside the phagolysosome and can control the immune activation of macrophages (MØs). Although MØs are highly active phagocytic cells with the capacity to destroy pathogens, they additionally comprise the host cells for Leishmania infection, replication, and stable establishment in the mammal host. The present study compares, for the first time, the innate immune response to L. infantum infection of two different macrophage lineages: the blood macrophages and the liver macrophages (Kupffer cells, KC). Our findings showed that L. infantum takes advantage of the natural predisposition of blood-MØs to phagocyte pathogens. However, parasites rapidly subvert the mechanisms of MØs immune activation. On the other hand, KCs, which are primed for immune tolerance, are not extensively activated and can overcome the dormancy induced by the parasite, exhibiting a selection of immune mechanisms, such as extracellular trap formation. Altogether, KCs reveal a different pattern of response in contrast with blood-MØs when confronting L. infantum parasites. In addition, KCs response appears to be more efficient in managing parasite infection, thus contributing to the ability of the liver to naturally restrain Leishmania dissemination.
AB - L. infantum is the aetiological agent of zoonotic visceral leishmaniasis (ZVL), a disease that affects humans and dogs. Leishmania parasites are well adapted to aggressive conditions inside the phagolysosome and can control the immune activation of macrophages (MØs). Although MØs are highly active phagocytic cells with the capacity to destroy pathogens, they additionally comprise the host cells for Leishmania infection, replication, and stable establishment in the mammal host. The present study compares, for the first time, the innate immune response to L. infantum infection of two different macrophage lineages: the blood macrophages and the liver macrophages (Kupffer cells, KC). Our findings showed that L. infantum takes advantage of the natural predisposition of blood-MØs to phagocyte pathogens. However, parasites rapidly subvert the mechanisms of MØs immune activation. On the other hand, KCs, which are primed for immune tolerance, are not extensively activated and can overcome the dormancy induced by the parasite, exhibiting a selection of immune mechanisms, such as extracellular trap formation. Altogether, KCs reveal a different pattern of response in contrast with blood-MØs when confronting L. infantum parasites. In addition, KCs response appears to be more efficient in managing parasite infection, thus contributing to the ability of the liver to naturally restrain Leishmania dissemination.
KW - Blood macrophages
KW - Innate immunity
KW - Kupffer cells
KW - Leishmania infantum
KW - Zoonotic visceral leishmaniasis
UR - http://www.scopus.com/inward/record.url?scp=85122804438&partnerID=8YFLogxK
U2 - 10.3390/biology11010100
DO - 10.3390/biology11010100
M3 - Article
C2 - 35053098
AN - SCOPUS:85122804438
VL - 11
JO - Biology
JF - Biology
IS - 1
M1 - 100
ER -