TCRβ-expressing macrophages induced by a pathogenic murine malaria correlate with parasite burden and enhanced phagocytic activity

• Published in: PloS one Vol. 13; no. 7; p. e0201043
• Main Authors: Oakley, Miranda S, Chorazeczewski, Joanna K, Aleshnick, Maya, Anantharaman, Vivek, Majam, Victoria, Chawla, Bhavna, Myers, Timothy G, Su, Qin, Okoth, Winter A, Takeda, Kazuyo, Akue, Adovi, KuKuruga, Mark, Aravind, L, Kumar, Sanjai
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.07.2018; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Adaptive systems; Animals; Atherosclerosis; Biology and Life Sciences; Brain; Brain - immunology; Brain - parasitology; Brain research; CD11b antigen; Correlation; Epitopes; Erythrocytes; Erythrocytes - parasitology; Fatalities; Fc receptors; Female; Food; Gene expression; Gene Expression Regulation; Gene Rearrangement; Genomics; Immune response; Immune system; Infections; Infectious diseases; Leukocytes - metabolism; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - parasitology; Malaria; Malaria, Cerebral - genetics; Malaria, Cerebral - immunology; Malaria, Cerebral - parasitology; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; National libraries; Parasitemia; Parasites; Pathogenesis; Phagocytes; Phagocytosis; Plasma membranes; Proteins; RAG1 protein; Receptors; Receptors, Antigen, T-Cell, alpha-beta - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; T cell receptors; T-cell receptor; Transcription; Transcription, Genetic; Tuberculosis; Vector-borne diseases; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0201043

Macrophages express a wide array of invariant receptors that facilitate host defense and mediate pathogenesis during pathogen invasion. We report on a novel population of CD11bhighCD14+F4/80+ macrophages that express TCRβ. This population expands dramatically during a Plasmodium berghei ANKA infection and sequesters in the brain during experimental cerebral malaria. Importantly, measurement of TCRβ transcript and protein levels in macrophages in wildtype versus nude and Rag1 knockout mice establishes that the observed expression is not a consequence of passive receptor expression due to phagocytosis or trogocytosis of peripheral T cells or nonspecific antibody staining to an Fc receptor or cross reactive epitope. We also demonstrate that TCRβ on brain sequestered macrophages undergoes productive gene rearrangements and shows preferential Vβ usage. Remarkably, there is a significant correlation in the proportion of macrophages that express TCRβ and peripheral parasitemia. In addition, presence of TCRβ on the macrophage also correlates with a significant increase (1.9 fold) in the phagocytosis of parasitized erythrocytes. By transcriptional profiling, we identify a novel set of genes and pathways that associate with TCRβ expression by the macrophage. Expansion of TCRβ-expressing macrophages points towards a convergence of the innate and adaptive immune responses where both arms of the immune system cooperate to modulate the host response to malaria and possibly other infections.