TCR[beta]-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: Public Library of Science 25.07.2018
• Subjects: Analysis; Gene expression; Macrophages; Malaria; T cells; Transcription factors
• 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 CD11b.sup.high CD14.sup.+ F4/80.sup.+ macrophages that express TCR[beta]. This population expands dramatically during a Plasmodium berghei ANKA infection and sequesters in the brain during experimental cerebral malaria. Importantly, measurement of TCR[beta] 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 TCR[beta] on brain sequestered macrophages undergoes productive gene rearrangements and shows preferential V[beta] usage. Remarkably, there is a significant correlation in the proportion of macrophages that express TCR[beta] and peripheral parasitemia. In addition, presence of TCR[beta] 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 TCR[beta] expression by the macrophage. Expansion of TCR[beta]-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.