Nematode-Induced Growth Factors Related to Angiogenesis in Autoimmune Disease Attenuation

Abstract

Accumulating data suggest an important role of growth factors in autoimmune diseases and parasitic nematode infections. Nematodes are used in clinical studies of autoimmune diseases and parasite-derived molecules are widely studied for their therapeutic potential in various types of disorders. However, the effect of nematode infection on growth factors in autoimmune disorders has not been studied. The objective of this study was to evaluate the influence of infection with the intestinal nematode Heligmosomoides polygyrus in murine autoimmune models on the production of growth factors. Here, the level of a variety of growth factors related mainly to angiogenesis was evaluated by protein array in the intestinal mucosa of C57BL/6 dextran sodium sulfate-induced colitic mice and in cerebral spinal fluid of experimental autoimmune encephalomyelitis (EAE) mice infected with nematodes. In addition, vessel formation was evaluated in the brains of EAE mice infected with H. polygyrus. A significant influence of nematode infection on the level of angiogenic factors was observed. Parasitic infection of colitic mice resulted in upregulation of mucosal AREG, EGF, FGF-2, and IGFBP-3 in the intestine of the host and better adaptation (infectivity). In EAE mice, infection increased the level of FGF-2 and FGF-7 in CSF. In addition, remodeling of brain vessels was observed, with a higher density of long vessels. Nematode-derived factors are promising tools to fight autoimmune diseases and to study angiogenesis.

Deciphering the Dual Role of Heligmosomoides polygyrus Antigens in Macrophage Modulation and Breast Cancer Cell Growth

“…Considering TGF-β’s role in tumor growth [ 49 , 50 ], the impact of Hp-TGM on cancer cells is a critical area for further research. Additionally, H. polygyrus infection in colitic mice has been linked to the upregulation of angiogenesis-related growth factors [ 51 ], suggesting that the parasite secretes compounds affecting cancer cell growth.…”

The transcriptional control of the VEGFA-VEGFR1 (FLT1) axis in alternatively polarized murine and human macrophages

“…On the other hand, other studies revealed that the alternatively polarized macrophages have proangiogenic capacity in vitro and in vivo ( 25 , 26 ). Thirdly, alternative macrophage polarization is often associated with pathological processes characterized by increased angiogenesis including tumor development and metastasis formation, parasite infections, or Th2-type airway inflammation and asthma ( 24 , 80 – 83 ). For instance, an important adaptation strategy of filarial parasites can be the induction of blood vessel formation following the infection ( 84 ).…”

“…For instance, an important adaptation strategy of filarial parasites can be the induction of blood vessel formation following the infection ( 84 ). Indeed, Heligmosomoides polygyrus infection enhanced the levels of several proangiogenic factors in cerebrospinal fluid and lead to new vessel formation in the brain ( 83 ). Using publicly available bulk RNA-seq and single-cell RNA-seq datasets from two different parasite infection models, we determined that the nematode infection-induced alternative macrophage polarization was linked to elevated Flt1 mRNA level and repressed Vegfa expression.…”

The Impact of Intestinal Inflammation on Nematode’s Excretory–Secretory Proteome

“…However, this therapeutic effect is accompanied by increased growth, survival, and reproduction of the parasite, as well as a much greater male-to-female ratio, all of which indicate adaptation of the parasite. This phenomenon was observed in a colitis model induced with dextran sulphate sodium (DSS) and is independent of the genetic background of the host [ 10 ]. Based on 2D proteomic analysis of the somatic antigens of L4-stage H. polygyrus that developed in colitic conditions, we observed strong differences in protein composition [ 11 ], and these changes were dependent of the sex of the nematode [ 12 ].…”