PMID- 37983293
OWN - NLM
STAT- MEDLINE
DCOM- 20231206
LR  - 20231217
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 17
IP  - 11
DP  - 2023 Nov
TI  - Impaired functions of human monocyte-derived dendritic cells and induction of 
      regulatory T cells by pathogenic Leptospira.
PG  - e0011781
LID - 10.1371/journal.pntd.0011781 [doi]
LID - e0011781
AB  - Leptospirosis is a global zoonosis caused by pathogenic Leptospira. The disease 
      outcome is influenced by the interplay between innate and adaptive immune 
      responses. Dendritic cells (DCs) play a crucial role in shaping the adaptive 
      immune response. A recent study revealed that pathogenic Leptospira limited the 
      activation of human monocyte-derived dendritic cells (MoDCs) compared to 
      non-pathogenic Leptospira, but their impact on T-cell responses has not been 
      investigated. Our study is the first to explore how viable pathogenic and 
      non-pathogenic Leptospira affect the interaction between human MoDCs and T cells. 
      We found that MoDCs infected with pathogenic leptospires (L. interrogans serovar 
      Pomona and a clinical isolate, MoDCs-P) exhibited lower levels of CD80 and CD83 
      expression, suggesting partially impaired MoDC maturation, induced regulatory T 
      cells (Tregs) while failing to induce CD4+ T cell proliferation, compared to 
      MoDCs infected with non-pathogenic leptospires (L. biflexa serovar Patoc and L. 
      meyeri serovar Ranarum, MoDCs-NP). In contrast, non-pathogenic leptospires 
      enhanced MoDC maturation and induced higher T cell proliferation including 
      IFN-gamma-producing CD4+ T cells, indicative of a Th1-type response. Furthermore, 
      pathogenic leptospires induced higher MoDC apoptosis through a cysteine aspartic 
      acid-specific protease-3 (caspase-3)-dependent pathway and upregulated expression 
      of the prostaglandin-endoperoxide synthase 2 (PTGS2) gene. Notably, prostaglandin 
      E2 (PGE2), a product of the PTGS2 pathway, was found at higher levels in the sera 
      of patients with acute leptospirosis and in the supernatant of MoDCs-P, possibly 
      contributing to Treg induction, compared to those of healthy donors and MoDCs-NP, 
      respectively. In conclusion, this study reveals a novel immunosuppressive 
      strategy employed by pathogenic Leptospira to evade host immunity by partially 
      impairing MoDC maturation and inducing Tregs. These findings deepen our 
      understanding of leptospirosis pathogenesis in humans and may provide a novel 
      strategy to modulate DCs for the prevention and treatment of the disease.
CI  - Copyright: (c) 2023 Krangvichian et al. 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.
FAU - Krangvichian, Pratomporn
AU  - Krangvichian P
AD  - Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn 
      University, Bangkok, Thailand.
FAU - Techawiwattanaboon, Teerasit
AU  - Techawiwattanaboon T
AD  - Department of Microbiology, Faculty of Medicine, Chulalongkorn University and 
      King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
AD  - Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine 
      Research and Development, Chulalongkorn University, Bangkok, Thailand.
FAU - Palaga, Tanapat
AU  - Palaga T
AD  - Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine 
      Research and Development, Chulalongkorn University, Bangkok, Thailand.
AD  - Department of Microbiology, Faculty of Science, Chulalongkorn University, 
      Bangkok, Thailand.
FAU - Ritprajak, Patcharee
AU  - Ritprajak P
AD  - Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive 
      Nanomaterials, Department of Microbiology, Faculty of Dentistry, Chulalongkorn 
      University, Bangkok, Thailand.
FAU - Kueanjinda, Patipark
AU  - Kueanjinda P
AD  - Department of Microbiology, Faculty of Medicine, Chulalongkorn University and 
      King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
FAU - Kaewraemruaen, Chamraj
AU  - Kaewraemruaen C
AD  - Department of Science and Bioinnovation, Faculty of Liberal Arts and Science, 
      Kasetsart University, Kamphaeng Saen Campus, Nakhon Pathom, Thailand.
FAU - Patarakul, Kanitha
AU  - Patarakul K
AUID- ORCID: 0000-0002-1781-7012
AD  - Department of Microbiology, Faculty of Medicine, Chulalongkorn University and 
      King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
AD  - Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine 
      Research and Development, Chulalongkorn University, Bangkok, Thailand.
LA  - eng
PT  - Journal Article
DEP - 20231120
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Humans
MH  - Monocytes
MH  - T-Lymphocytes, Regulatory
MH  - *Leptospira
MH  - Cyclooxygenase 2/genetics/metabolism
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - *Leptospirosis/metabolism
MH  - Dendritic Cells
PMC - PMC10695387
COIS- The authors have declared that no competing interests exist.
EDAT- 2023/11/20 18:43
MHDA- 2023/12/06 06:42
PMCR- 2023/11/20
CRDT- 2023/11/20 13:53
PHST- 2023/04/17 00:00 [received]
PHST- 2023/11/08 00:00 [accepted]
PHST- 2023/12/04 00:00 [revised]
PHST- 2023/12/06 06:42 [medline]
PHST- 2023/11/20 18:43 [pubmed]
PHST- 2023/11/20 13:53 [entrez]
PHST- 2023/11/20 00:00 [pmc-release]
AID - PNTD-D-23-00469 [pii]
AID - 10.1371/journal.pntd.0011781 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2023 Nov 20;17(11):e0011781. doi: 
      10.1371/journal.pntd.0011781. eCollection 2023 Nov.