Functional Impairment of Murine Dendritic Cell Subsets following Infection with Infective Larval Stage 3 of Brugia malayi

• Published in: Infection and immunity 2017-01, Vol.85 (1)
• Main Authors: Sharma, Aditi, Sharma, Pankaj, Vishwakarma, Achchhe Lal, Srivastava, Mrigank
• Format: Article
• Language: English
• Subjects: Animals; Brugia malayi; Brugia malayi - pathogenicity; CD8-Positive T-Lymphocytes - metabolism; Cell Proliferation - physiology; Dendritic Cells - metabolism; Dendritic Cells - parasitology; Dendritic Cells - pathology; Down-Regulation - physiology; Filariasis - metabolism; Filariasis - parasitology; Filariasis - pathology; Fungal and Parasitic Infections; Interleukin-10 - metabolism; Interleukin-12 - metabolism; Interleukin-4 - metabolism; Larva - parasitology; Lymphocyte Activation - physiology; Mice; Mice, Inbred BALB C; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Protein Tyrosine Phosphatase, Non-Receptor Type 2 - metabolism; Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism; PTEN Phosphohydrolase - metabolism; Toll-Like Receptors - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00818-16

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.