Kinetics of Cellular Responses to IntraperitonealBrugia pahangiInfections in Normal and Immunodeficient Mice

Abstract

Filarial infections evoke exuberant inflammatory responses in the peritoneal cavities of immunocompetent mice. Clearance of infection appears to be dependent on complex interactions between B1 and B2 B lymphocytes, T cells, eosinophils, macrophages, and the products of these cells. In an earlier communication, we described the course of infection in normal immunocompetent mice. In this study, we utilize mice with well-characterized mutations that disable one or more effector components of adaptive immunity in order to determine their roles in host protection. We characterize peritoneal exudate cells by flow cytometry and determine the kinetics of accumulation of each of the different cell types following infection with Brugia pahangi. We find that (i) fourcolor flow-cytometric analysis of peritoneal exudate cells using anti-CD3, -CD11b, -CD19, and -Gr1 can distinguish up to six different populations of cells; (ii) an initial influx of neutrophils occurs within 24 h of infection, independent of the adaptive immune status of mice, and these cells disappear by day 3; (iii) an early influx of eosinophils is seen at the site of infection in all strains studied, but a larger, second wave occurs only in mice with T cells; (iv) the presence of T cells and eosinophils is important in causing an increase in macrophage size during the course of infection; and (v) most unexpectedly, T-cell recruitment appears to be optimal only if B cells are present, since JHD mice recruit significantly fewer T cells to the site of infection.Mammalian immune responses are remarkably different for different classes of infectious agents. The ensuing inflammatory reaction takes shape with differential recruitment of a variety of cells of the adaptive and innate immune systems. Microorganisms (bacteria and viruses) may be effectively combated by mechanisms such as phagocytosis, neutralization by antibodies, and elimination of infected cells by cytotoxicity. The rules that govern the orchestration of the immune response to and the elimination of large multicellular parasites remain largely unknown. While parasites such as gastrointestinal nematodes can be expelled alive from the body by various mechanisms (5, 6), tissue-dwelling parasites such as filarial nematodes need to be immobilized, sequestered, killed, and disposed of to achieve complete clearance.Filarial parasites are large, metazoan, tissue-dwelling organisms that cause diseases such as lymphatic filariasis, which afflicts over 120 million people in the world (14). Over the past several years, we have used murine models to understand the factors that contribute to host defense. Infection with the feline filarial parasite Brugia pahangi in the peritoneal cavities of laboratory mice evokes an inflammatory reaction. In a recent publication (17), Rajan et al. detailed the time course of Brugia infection in normal, immunocompetent mice and the cellular responses in the peritoneal cavities of these mice. The intent was to use these data to begin to analyze the deviations from such normalcy ...

Critical Role for IgM in Host Protection in Experimental Filarial Infection

“…Naive or day 14 Brugia-primed PECs were harvested from B6 wt mice and stained for CD11b, CD19, CD3, and IgM. Different cell populations were identified as previously described (2,12). IgM expression on the surface of various cell types is represented as an offset histogram overlay.…”

“…In an attempt to understand host protective mechanisms, we have analyzed the kinetics of the host response to the i.p. injection of infective brugian larvae (1,2). We have shown that infection is followed by an exuberant inflammatory response, resulting in the accumulation of ϳ10 times as many leukocytes as are present in naive mice.…”

“…Histologically, these aggregates are composed predominately of macrophages (some of which fuse to form multinucleated giant cells) and eosinophils. These multilayered structures are referred to as granulomas in the pathology literature (1,2). Granulomas with a striking histological resemblance to that described in the murine i.p.…”

Expansion of Foxp3+ Regulatory T Cells in Mice Infected with the Filarial Parasite Brugia malayi

“…Finally, in a parasite closely related to B. malayi (B. pahangi), restimulation of splenocytes from infected mice expanded a population of CD25 worms transplanted into the peritoneal cavity live for 2-3 mo (34), in both cases inducing a highly polarized Th2 response (30,32,35). Moreover, infection of either stage into the peritoneal cavity results in a recruitment of well-characterized leukocyte populations (33), including suppressive alternatively activated macrophages (36). Within this timeframe, therefore, infection of mice with the human parasite sheds invaluable light on how the mammalian immune response reacts to, and may be manipulated by, filarial infections.…”

A peçonha do escorpião Tityus serrulatus é reconhecida por receptores de reconhecimento padrão e induz ativação celular e inflamação

“…Nós observamos que houve aumento de células positivas para os marcadores GR1, F4/80, CD3, CD4 e CD8 após a injeção de Ts2 ou Ts6. Estes são os marcadores de superfície comuns utilizados para caracterizar os neutrófilos (GR1), macrófagos (F4/80), linfócitos CD4 (CD3/CD4) e linfócitos CD8 (CD3/CD8), respectivamente (RAMALINGAM et al, 2003;PILLAI et al, 2009). …”