Induction of IL-10 and TGFβ from CD4+CD25+FoxP3+ T Cells Correlates with Parasite Load in Indian Kala-azar Patients Infected with Leishmania donovani

• Published in: PLoS neglected tropical diseases 2016-02, Vol.10 (2), p.e0004422-e0004422
• Main Authors: Bhattacharya, Pradyot, Ghosh, Smriti, Ejazi, Sarfaraz Ahmad, Rahaman, Mehebubar, Pandey, Krishna, Ravi Das, Vidya Nand, Das, Pradeep, Goswami, Rama Prosad, Saha, Bibhuti, Ali, Nahid
• Format: Article
• Language: English
• Subjects: Adult; Biology and Life Sciences; Case-Control Studies; CD4 Antigens - genetics; CD4 Antigens - immunology; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - immunology; Humans; India - ethnology; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-2 Receptor alpha Subunit - genetics; Interleukin-2 Receptor alpha Subunit - immunology; Leishmania donovani; Leishmania donovani - immunology; Leishmania donovani - physiology; Leishmaniasis, Visceral - ethnology; Leishmaniasis, Visceral - genetics; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - parasitology; Male; Medicine and Health Sciences; Parasite Load; Research and Analysis Methods; T-Lymphocytes, Regulatory - immunology; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - immunology; Young Adult
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0004422

Visceral leishmaniasis (VL) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. However, the direct association between different immunological correlates and parasite numbers remains largely unknown. We examined the plasma levels of different disease promoting/protective as well as Th17 cytokines and found IL-10, TGFβ and IL-17 to be significantly correlated with parasite load in VL patients (r = 0.52, 0.53 and 0.51 for IL-10, TGFβ and IL-17, respectively). We then extended our investigation to a more antigen-specific response and found leishmanial antigen stimulated levels of both IL-10 and TGFβ to be significantly associated with parasite load (r = 0.71 and 0.72 for IL-10 and TGFβ respectively). In addition to cytokines we also looked for different cellular subtypes that could contribute to cytokine secretion and parasite persistence. Our observations manifested an association between different Treg cell markers and disease progression as absolute numbers of CD4+CD25+ (r = 0.55), CD4+CD25hi (r = 0.61) as well as percentages of CD4+CD25+FoxP3+ T cells (r = 0.68) all correlated with parasite load. Encouraged by these results, we investigated a link between these immunological components and interestingly found both CD4+CD25+ and CD4+CD25+FoxP3+ Treg cells to secrete significantly (p