Ticks, Ixodes scapularis, Feed Repeatedly on White-Footed Mice despite Strong Inflammatory Response: An Expanding Paradigm for Understanding Tick–Host Interactions

Abstract

Ticks transmit infectious agents including bacteria, viruses and protozoa. However, their transmission may be compromised by host resistance to repeated tick feeding. Increasing host resistance to repeated tick bites is well known in laboratory animals, including intense inflammation at the bite sites. However, it is not known whether this also occurs in wild rodents such as white-footed mice, Peromyscus leucopus, and other wildlife, or if it occurs at all. According to the “host immune incompetence” hypothesis, if these mice do not have a strong inflammatory response, they would not reject repeated tick bites by Ixodes scapularis. To test this hypothesis, histopathological studies were done comparing dermal inflammation in P. leucopus versus guinea pigs, Cavia porcellus, repeatedly infested with I. scapularis. In P. leucopus, the immune cell composition was like that seen in laboratory mouse models, with some differences. However, there was a broad sessile lesion with intact dermal architecture, likely enabling the ticks to continue feeding unimpeded. In contrast, in C. porcellus, there was a relatively similar mixed cellular profile, but there also was a large, leukocyte-filled cavitary lesion and scab-like hyperkeratotic changes to the epidermal layer, along with itching and apparent pain. Ticks attached to sensitized C. porcellus fed poorly or were dislodged, presumably due to the weakened anchoring of the tick’s mouthparts cemented in the heavily inflamed and disintegrating dermal tissues. This is the first time that the architecture of the skin lesions has been recognized as a major factor in understanding tick–host tolerance versus tick bite rejection. These findings broadly strengthen previous work done on lab animal models but also help explain why I. scapularis can repeatedly parasitize white-footed mice, supporting the “immune evasion theory” but cannot repeatedly parasitize other, non-permissive hosts such as guinea pigs.

Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non‐sensitized mice reveals saliva‐dependent and immune‐dependent phenotypes

“…In addition, we observed increased T‐cell numbers in the bronchoalveolar lavage fluid but not in the lung tissue of bite‐sensitized mice challenged with the mosquito SGE . Many other works have shown the presence of eosinophils in the arthropod bite site of different host species . Of note, the proportion of eosinophils and neutrophils in the skin following bite may vary depending on the haematophagous arthropod studied, on the vertebrate host species and on their immune status (naïve versus immune/sensitized), a finding also observed in our study.…”

Wonders of tick saliva

“…Reviews on the discovery of proteins in tick saliva and their characterisation include: Steen et al, 2006;Murfin and Fikrig, 2017;Šimo et al, 2017. Many studies involve tick feeding on laboratory hosts that the particular tick species would not encounter naturally, hence limiting interpretation of the results as host species affects expression of saliva proteins and feeding success (Wang et al, 2001b;Anderson et al, 2017;Tirloni et al, 2017).…”

“…This hypothesis is compatible with male versus female differences in saliva molecules and male and female co-feeding post-copulation (section 2.6), and with the pooling of sialomes through aggregated feeding (section 2.5). Nevertheless, the ability of certain natural hosts to tolerate repeated tick infestations while atypical hosts reject them, challenges this hypothesis (Ribeiro, 1989;Dizij and Kurtenbach, 1995;Carvalho et al, 2014;Anderson et al, 2017). Bioinformatic analysis suggests tick miRNAs are similarly redundant: many target genes in the same host pathway appear to be regulated by more than one saliva-specific miRNA (Hackenberg et al, 2017).…”

Tick and Host Derived Compounds Detected in the Cement Complex Substance

“…Ixodid ticks feed on blood for a relatively long period and an evolutionary adaptation to overcome host inflammatory and immune responses using molecules produced in tick salivary glands or recycled from the host and inoculated with saliva into the feeding site [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Cattle tick Rhipicephalus microplus (Canestrini, 1888) is an Ixodid one-host tick species (all developmental stages remain on the same host) with an impact on cattle industry in tropical and subtropical regions of the world [3,9,10].…”