Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 4 their response to Brucella and Tremocostus is quite special and will produce different immune substances and signals. It is precisely because of these differences that they show different resistance when facing certain diseases (Zhang et al., 2017; Grandoni et al., 2023). 4 Mechanisms of Host-Pathogen Interactions 4.1 Pathogen recognition and immune activation When water buffalo are infected with parasites like giant hepatic flukesomiae, schistosomiae, their immune systems begin to work. The “front line defense” in the buffalo’s body-the innate immune system, will first recognize the pathogen. They discover these invaders by identifying special molecules called “PAMPs” (Mabbott, 2018). These molecules are usually only found in pathogens such as bacteria and parasites. During infection, water buffalo produce special “signal molecules” such as IFN-γ, IL-4 and IL-10. These substances can make the immune system more active or converge, helping the body regulate the intensity of the response. If it is infected with giant hepatic flukes, these molecules will change differently at different times, indicating that the body has been working hard to deal with the pathogen. After infection with Schistosoma japanese, specific antibodies to the larval stage will be quickly produced in the buffalo, indicating that their immune system can recognize and respond in a timely manner. 4.2 Evasion strategies employed by pathogens However, not all pathogens will be easily defeated. Some parasites like giant tidalis are smart, and they learn to “pretend to be stupid” or “hide” to escape the buffalo’s immune system. At the beginning, water buffalo will develop an immune response to these bugs called Th2, a common way to fight parasites. But this reaction will soon be “suppressed” by the parasite, making the immune system less intense. This is because parasites reduce pro-inflammatory molecules and make the body more “tolerant” so that they can stay in the body for a long time without being removed (Zhang et al., 2017). There are similar ways to escape from schistosomiae. They bind to some antibodies in the buffalo, so that they can "disguise" themselves and are not easily seen by immune cells (Hosking et al., 2015). These clever strategies allow pathogens to survive in water buffalo for a long time. 4.3 Immune signaling pathways and cytokine responses When water buffalo are infected with pathogens, there are many changes in the immune signal in the body. These changes are accomplished through different cytokines. For example, when infected with giant tidalis, the buffalo’s body will show an inhibitory reaction at the beginning, and the level of TGF-β will increase, which is actually helping the parasite to “set up” better. Gradually, the buffalo's immune response will become a “mixed type”, that is, both Th1 and Th2 types of reactions. Later, the reaction tends toward Th1 and Treg, which makes the infection persistent (Shi et al., 2017). When infected with giant hepatic flukes, whether it is the first infection or the second infection, the buffalo’s Th2 reaction is very strong, while the Th1 type has almost no changes. This shows that the buffalo’s immune system has a relatively stable response pattern to this pathogen (Meng et al., 2023). These reaction patterns help us better understand how buffalo deals with pathogens, and also provide direction for the future development of treatment and prevention and control methods. 5 Genetic and Molecular Insights into Immune Response 5.1 Identification of immune-related genes and markers Scientists have found many genes and markers related to buffalo immunity. These genes play a key role in buffalo's resistance to bacteria and parasites. For example, when water buffalo are infected with giant hepatic flukes, the activity of some genes responsible for immunity (such as cytokines and transcription factors) in the body changes. This suggests that they have an effect on immune response (Shi et al., 2017; Wang, 2024). In addition, during the study of buffalo infection with circular Taylorworm, the performance of genes such as MHC (main histocompatibility complex) and TLR (Toll-like receptor) were also examined. However, these genes did not change significantly in that infection, which may indicate that they have little effect on combating this pathogen. Through genome comparison, the study also found that NOD-like receptors (NLRs) in water buffalo are very important for identifying bacteria. They can detect bacteria at the first time and initiate an immune response (Brahma et al., 2015).
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