Metabolomic changes associated with acquired resistance to Ixodes scapularis

Area of Science:

• Immunology
• Parasitology
• Metabolomics

Background:

• Guinea pigs develop acquired resistance to Ixodes scapularis (ATR) after repeated exposure.
• The molecular mechanisms underlying ATR are not fully understood but involve immune responses to tick saliva proteins.
• Tick saliva can alter host metabolism, influencing the development of resistance.

Purpose of the Study:

• To investigate the changes in the serum metabolome during the development of ATR in guinea pigs.
• To explore the role of the tyrosine metabolic pathway in ATR.
• To evaluate the potential of targeting the tyrosine metabolism pathway for controlling Ixodes scapularis.

Main Methods:

• Analysis of guinea pig serum metabolome during ATR development.
• Administration of hydroxyphenyllactic acid (HPLA) to mice, which do not naturally develop ATR.
• Administration of nitisinone, a tyrosine degradation inhibitor, to mice.
• Exposure of treated mice to Ixodes scapularis and assessment of tick mortality.

Main Results:

• Induction of hydroxyphenyllactic acid (HPLA) and other tyrosine metabolic pathway components were associated with ATR in guinea pigs.
• Administration of HPLA to mice resulted in 26% Ixodes scapularis mortality.
• Administration of nitisinone to mice resulted in 72% Ixodes scapularis mortality, compared to 2% in control mice.

Conclusions:

• Tick bites induce significant alterations in the host metabolome.
• The tyrosine metabolic pathway is a key factor in the host-tick interaction and the development of acquired tick resistance.
• Targeting the tyrosine metabolism pathway presents a promising strategy for the control of Ixodes scapularis infestations.