TY - JOUR
T1 - Malnutrition exacerbates pathogenesis of Lutzomyia longipalpis sand fly-transmitted Leishmania donovani
AU - Iniguez, Eva
AU - Doehl, Johannes
AU - Cecilio, Pedro
AU - Serafim, Tiago Donatelli
AU - Percopo, Caroline
AU - Rangel-Gonzalez, Yvonne
AU - Dey, Somaditya
AU - Osorio, Elvia J.
AU - Huffcutt, Patrick
AU - Roitman, Sofia
AU - Meneses, Claudio
AU - Short, Mara
AU - Valenzuela, Jesus G.
AU - Melby, Peter C.
AU - Kamhawi, Shaden
N1 - Publisher Copyright:
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Visceral leishmaniasis (VL) is transmitted by Leishmania-infected sand fly bites and malnutrition is a known risk factor in human VL. Models using sand fly transmission or malnutrition promote parasite dissemination. By investigating features of L. donovani-Lutzomyia longipalpis transmission to malnourished mice, we show that a comparable IL1-β-driven acute inflammation is maintained in malnourished (MN-SF) and well-nourished (WN-SF) sand fly-infected mice. However, parasite dissemination was more pronounced in MN-SF that had a significantly higher acute (P ≤ 0.001) and chronic (P ≤ 0.0001) splenic parasite burden compared to WN-SF. Compared to WN-SF, MN-SF exhibited chronic clinical symptoms (P ≤ 0.0001), neutrophilia (P ≤ 0.001), lymphocytopenia (P ≤ 0.0001), increased heme oxygenase-1 (P ≤ 0.001) and IL17-A (P ≤ 0.0001) levels, dysregulation of liver enzymes, lymph node barrier dysfunction, and augmented dysbiosis, all associated with enhanced VL severity. Combining vector-transmission and malnutrition provides an improved model to study VL pathogenesis and host defense.
AB - Visceral leishmaniasis (VL) is transmitted by Leishmania-infected sand fly bites and malnutrition is a known risk factor in human VL. Models using sand fly transmission or malnutrition promote parasite dissemination. By investigating features of L. donovani-Lutzomyia longipalpis transmission to malnourished mice, we show that a comparable IL1-β-driven acute inflammation is maintained in malnourished (MN-SF) and well-nourished (WN-SF) sand fly-infected mice. However, parasite dissemination was more pronounced in MN-SF that had a significantly higher acute (P ≤ 0.001) and chronic (P ≤ 0.0001) splenic parasite burden compared to WN-SF. Compared to WN-SF, MN-SF exhibited chronic clinical symptoms (P ≤ 0.0001), neutrophilia (P ≤ 0.001), lymphocytopenia (P ≤ 0.0001), increased heme oxygenase-1 (P ≤ 0.001) and IL17-A (P ≤ 0.0001) levels, dysregulation of liver enzymes, lymph node barrier dysfunction, and augmented dysbiosis, all associated with enhanced VL severity. Combining vector-transmission and malnutrition provides an improved model to study VL pathogenesis and host defense.
UR - https://www.scopus.com/pages/publications/105005112529
UR - https://www.scopus.com/pages/publications/105005112529#tab=citedBy
U2 - 10.1038/s42003-025-08106-8
DO - 10.1038/s42003-025-08106-8
M3 - Article
C2 - 40360769
AN - SCOPUS:105005112529
SN - 2399-3642
VL - 8
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 746
ER -