Serum cytokine responses in Rickettsia felis infected febrile children, Ghana

Abstract

The intracellular pathogen Rickettsia felis causes flea-borne spotted fever and is increasingly recognized as an emerging cause of febrile illness in Africa, where co-infection with Plasmodium falciparum is common. Rickettsiae invade endothelial cells. Little is known, however, about the early immune responses to infection. In this study, we characterize for the first time the cytokine profile in the acute phase of illness caused by R. felis infection, as well as in plasmodial co-infection, using serum from 23 febrile children < 15 years of age and 20 age-matched healthy controls from Ghana. Levels of IL-8 (interleukin-8), IP-10 (interferon-γ-induced protein-10), MCP-1 (monocyte chemotactic protein-1), MIP-1α (macrophage inflammatory protein-1α) and VEGF (vascular endothelial growth factor) were significantly elevated in R. felis mono-infection; however, IL-8 and VEGF elevation was not observed in plasmodial co-infections. These results have important implications in understanding the early immune responses to R. felis and suggest a complex interplay in co-infections.

Surveillance of NK cell subsets and cytokine profile in patients with Rocky Mountain Spotted Fever

“…Levels of IL-8, IP-10, MCP-1 and MIG showed a significantly high increase in patients upon admission compared to the controls. These chemokine levels are consistent with those reported in pediatric patients infected with R. felis during the acute phase, where IL-8, IP-10, and MCP-1 attract immune cells to infection sites and likely reflect initial host responses to R. rickettsii (8). Plasma levels of IL-10, a potent inhibitor of TNFα and IL-6, were found to be significantly increased in patients upon admission to hospital.…”

“…In the present pilot study, it was observed that in pediatric patients with RMSF it was characterized by a systemic increase in several pro-inflammatory cytokines such as IL-6 and IL-8. This increase has also been reported in other studies of patients with RMSF (8,18,19) reflecting the activation of monocytes / macrophages and endothelial cells infected by rickettsia, and attraction of T and NK lymphocytes (20,21).…”

“…Rickettsia invades endothelial cells promoting their dissemination and causing vasculitis that stimulates cell signaling cascades, which leads to cytokine secretion, initiating infiltration into the vascular cell wall and perivascular space of macrophages, CD8 + T lymphocytes, CD4 + T lymphocytes and NK cells [6]. In human in vitro models, endothelial cells increase the expression and secretion of cytokines IL-1 (interleukin-1), IL-6 and TNFα (tumor necrosis factor α); chemokines such as CXCL8 / IL-8 (interleukin-8), CXCL10 / IP-10 (interferon gamma-induced protein 10), CCL2 / MCP-1 (monocyte chemoattractant protein 1), CXCL9 / MIG (interferon gamma-induced monokine) and CCL5 / RANTES that lead to the activation and recruitment of monocytes, NK cells (natural killers) and T lymphocytes to the site of infection leading to the potentiation of the inflammatory response and its elimination [7][8][9][10][11]. Monocytes, immature macrophages that circulate in the bloodstream, when infected promote the spread of the pathogen in the vascular endothelium, causing an increase in microvascular permeability leading to rickettsial vasculitis [12][13][14].…”

Immune monitoring of pediatric patients co-infected with Rickettsia rickettsii and Ehrlichia canis

“…Coinfections make the diagnosis a challenge; they assert the clinical status of the patient, complicate the treatment, and presumably, in some cases, they work in a symbiotic way or are synergistic (16,17,24). A few cases of coinfections with rickettsial diseases have been reported in Mexico, as reported by In contrast to results obtained by Rauch et al, 2018 in our study a significant difference was found between the co-infected and mono-infected groups, in which R. rickettsii was involved; this could be as a result of the aforementioned, which in some cases of co-infection, the mechanism of action of the pathogens involved boost or act synergistically, increasing the extent of the injury, severity, and complexity of the clinical picture.…”