title: Functional Impairment of Murine Dendritic Cell Subsets following Infection with Infective Larval Stage 3 of Brugia malayi.
abstract: Filarial parasites cause functional impairment of host dendritic cells (DCs). However, the effects of early infection on individual DC subsets are not known. In this study, we infected BALB/c mice with infective stage 3 larvae of the lymphatic filarial parasite Brugia malayi (Bm-L3) and studied the effect on fluorescence-activated cell sorter (FACS)-sorted DC subsets. While myeloid DCs (mDCs) accumulated by day 3 postinfection (p.i.), lymphoid DCs (LDCs) and CD8+plasmacytoid DCs (pDCs) peaked at day 7 p.i. in the spleens and mesenteric lymph nodes (mLNs) of infected mice. Increased tumor necrosis factor alpha (TNF-α) but reduced interleukin 12 (IL-12) and Toll-like receptor 4 (TLR4), -6, and -9 and reciprocal secretion of IL-4 and IL-10 were also observed across all DC subsets. Interestingly, Bm-L3 increased the expression of CD80 and CD86 across all DC subsets but decreased that of major histocompatibility complex class II (MHC-II) on mDCs and pDCs, resulting in their impaired antigen uptake and presentation capacities, but maximally attenuated the T-cell proliferation capacity of only mDCs. Furthermore, Bm-L3 increased phosphorylated p38 (p-p38), but not p-ERK, in mDCs and LDCs but downregulated them in pDCs, along with differential modulation of protein tyrosine phosphatases SHP-1, TCPTP, PTEN, and PTP1B across all DC subsets. Taken together, we report hitherto undocumented effects of early Bm-L3 infection on purified host DC subsets that lead to their functional impairment and attenuated host T-cell response.
authors: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, India.|Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors: Aditi
authors: A
authors: Sharma
authors: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors: Pankaj
authors: P
authors: Sharma
authors: Sophisticated Analytical Instrument Facility (SAIF), CSIR-Central Drug Research Institute, Lucknow, India.
authors: Achchhe Lal
authors: AL
authors: Vishwakarma
authors: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, India mrigank_srivastava@cdri.res.in.|Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors: Mrigank
authors: M
authors: Srivastava
mesh_terms: D000818:Animals; D017178:Brugia malayi / Q000472:pathogenicity*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology*; D015536:Down-Regulation / Q000502:physiology; D005368:Filariasis / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007814:Larva / Q000469:parasitology*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C516609:Ptpn1 protein, mouse; C509248:Ptpn6 protein, mouse; D051059:PTEN Phosphohydrolase
keywords: MAP kinases; Toll-like receptors; filariasis; flow cytometry; lymphoid dendritic cells; myeloid dendritic cells; plasmacytoid dendritic cells