PMID- 30248443 OWN - NLM STAT- MEDLINE DCOM- 20190927 LR - 20190927 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 129 DP - 2018 Dec TI - Impact of Trypanosoma cruzi infection on nitric oxide synthase and arginase expression and activity in young and elderly mice. PG - 227-236 LID - S0891-5849(18)30928-6 [pii] LID - 10.1016/j.freeradbiomed.2018.09.031 [doi] AB - Elderly organisms are more susceptible to infectious diseases. However, the impact of aging on antiparasitic mechanisms, especially the nitric oxide pathway, is poorly understood. Using an integrated in vivo and in vitro model, we compared the severity of Trypanosoma cruzi infection in young and elderly (8 or 72 weeks old) mice. Forty C57BL/6 mice were randomized into four groups: Y-inf, young infected; Yn-inf, young uninfected; A-inf, aged infected; An-inf, aged uninfected. Parasitemia was measured daily, and animals were euthanized after 15 days of infection. Trypanosoma cruzi-induced inflammatory processes were analyzed in blood and heart samples, as well as in bone marrow-derived macrophages (BMDMs) co-cultured with splenocytes isolated from young or elderly mice. Our results indicated upregulated IgG2b and IL-17 production in elderly animals, which was not sufficient to reduce parasitemia, parasitic load and myocarditis to levels observed in young animals. The higher susceptibility of elderly mice to T. cruzi infection was accompanied by reduced cardiac inducible nitric oxide synthase (iNOS) gene expression, nitric oxide (NO) and IFN-gamma levels, as well as an antagonistic upregulation of arginase-1 expression and arginase activity. The same responses were observed when BMDMs co-cultured with splenocytes from elderly mice were stimulated with T. cruzi antigens. Our findings indicate that elderly mice were more susceptible to T. cruzi infection, which was potentially related to an attenuated response to antigenic stimulation, inhibition of iNOS gene expression and NO production, and antagonistic upregulation of arginase gene expression and activity, which created favorable conditions for heart parasitism and myocarditis development. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Felizardo, Amanda A AU - Felizardo AA AD - Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil. FAU - Caldas, Ivo S AU - Caldas IS AD - Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil; Department of Pathology and Parasitology, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil. FAU - Mendonca, Andrea A S AU - Mendonca AAS AD - Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil; Department of Microbiology and Immunology, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil. FAU - Goncalves, Reggiani V AU - Goncalves RV AD - Department of Animal Biology, Federal University of Vicosa, Vicosa 36570-000, Minas Gerais, Brazil. FAU - Tana, Fernanda L AU - Tana FL AD - Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil; Department of Microbiology and Immunology, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil. FAU - Almeida, Leonardo A AU - Almeida LA AD - Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil; Department of Microbiology and Immunology, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil. FAU - Novaes, Romulo D AU - Novaes RD AD - Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil; Department of Structural Biology, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil. Electronic address: romulo.novaes@unifal-mg.edu.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180921 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (Antigens, Protozoan) RN - 0 (IFNG protein, mouse) RN - 0 (IL10 protein, mouse) RN - 0 (Il17a protein, mouse) RN - 0 (Immunoglobulin G) RN - 0 (Interleukin-17) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - EC 3.5.3.1 (Arg1 protein, mouse) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Aging/*genetics/immunology MH - Animals MH - Antigens, Protozoan/pharmacology MH - Arginase/blood/*genetics MH - Chagas Cardiomyopathy/*genetics/immunology/parasitology MH - Chagas Disease/*genetics/immunology/parasitology MH - Coculture Techniques MH - Gene Expression Regulation MH - Heart/parasitology MH - Host-Pathogen Interactions/genetics/immunology MH - Immunoglobulin G/blood/genetics MH - Interferon-gamma/blood/genetics MH - Interleukin-10/blood/genetics MH - Interleukin-17/blood/genetics MH - Macrophages/drug effects/immunology/parasitology MH - Mice MH - Mice, Inbred C57BL MH - Nitric Oxide Synthase Type II/blood/*genetics MH - Parasitemia/*genetics/immunology MH - Severity of Illness Index MH - Signal Transduction MH - T-Lymphocytes/drug effects/immunology/parasitology MH - Trypanosoma cruzi/immunology/*pathogenicity OTO - NOTNLM OT - Aging OT - Chagas disease OT - Experimental parasitology OT - Immunological response OT - Nitric oxide EDAT- 2018/09/25 06:00 MHDA- 2019/09/29 06:00 CRDT- 2018/09/25 06:00 PHST- 2018/05/27 00:00 [received] PHST- 2018/08/21 00:00 [revised] PHST- 2018/09/20 00:00 [accepted] PHST- 2018/09/25 06:00 [pubmed] PHST- 2019/09/29 06:00 [medline] PHST- 2018/09/25 06:00 [entrez] AID - S0891-5849(18)30928-6 [pii] AID - 10.1016/j.freeradbiomed.2018.09.031 [doi] PST - ppublish SO - Free Radic Biol Med. 2018 Dec;129:227-236. doi: 10.1016/j.freeradbiomed.2018.09.031. Epub 2018 Sep 21.