Immune Evasion strategies and phagocytosis.
Plasmodium falciparum and infected erythrocytes employ
diverse evasion
tactics to evade phagocytosis and the human immune system. One of the
key mechanisms is the recruitment of complement regulatory molecules,
such as factor H (FH), to IEs or parasite surfaces to inhibit complement
activation and subsequent lysis, highlighting the dual role of the
complement system in parasite infection [70,71] (Figure 3) .
Additionally, at late infection stages, P. falciparum utilizes surface
proteins such as SERA5 and SE36 to interact with host proteins such as
vitronectin (VTN), thereby preventing phagocytosis of the parasite and
IEs [72]. Plasmodium falciparum -infected erythrocytes (IEs)
have been found to express surface antigens such as RIFIN, interact with
inhibitory immune receptors, suppress host immune cell activation, and
utilize multiple immune evasion mechanisms [52]. Furthermore,Plasmodium falciparum evades phagocytosis through
VAR2CSA-mediated interactions with host cells and immune components,
ensuring its survival and persistence during placental malaria [73].
Additionally, Plasmodium falciparum evades phagocytosis by
inducing Kupffer cell apoptosis in the pre-erythrocytic stage and
interfering with macrophage phagocytic functions using hemozoin in the
erythrocytic stage [74,75]. These collective strategies aid in
evading the phagocytosis process through antigenic variation,
sequestration, and blocking of antibodies, which contributes to the
parasite’s ability to evade phagocytosis and survive within the host.
Therapeutic potential of phagocytosis in P. falciparum
infection.
The phagocytic mechanisms and responses in vaccine development for P.
falciparum infection have substantially improved. Studies have
highlighted the importance of DNA vaccination against PfRH5-inducingPlasmodium falciparum -specific neutralizing antibodies and T-cell
responses, highlighting a promising strategy for vaccine development
targeting phagocytic responses [76]. Vaccines targeting merozoite
proteins on ring-infected and uninfected erythrocytes can enhance
phagocytic responses, aiming to control parasitemia and prevent clinical
malaria in P. falciparum infections [65]. Additionally, acceleratedPlasmodium falciparum sporozoite chemoprophylaxis regimens induce
strong T-cell and antibody responses, potentially enhancing vaccine
efficacy by targeting phagocytic responses against malaria infection
[77]. Studies have indicated that vaccine development by focusing on
phagocytic responses to Plasmodium falciparum infection can be supported
through the use of a topical adjuvant with a TLR7 agonist, such as
imiquimod, to enhance humoral immunity [78]. A liposomal adjuvant
system, which induces robust antibody and CD8+ T-cell responses against
Plasmodium falciparum, also highlights the potential role of phagocytic
responses in malaria vaccine progress [79]. Furthermore, the
approach of phagocytic response stimulation in vaccine development aims
to induce protective immunity by neutralizing parasite infectivity and
has been investigated using a synthetic vaccine against Plasmodium
falciparum targeting the dominant epitope (NANP)3 [80]. These
advancements underscore the need to investigate the phagocytic approach
required for successful vaccine development against P. falciparum
infections.
A complete understanding of the phagocytic mechanisms against infected
erythrocytes and Plasmodium falciparum molecules, the role of
phagocyte cells, and the autophagy process in Plasmodium survival is
crucial for malaria treatment and includes several challenges and
limitations. Phagocytosis of infected and uninfected erythrocytes is
essential, but discriminating between them and staining the early ring
stages represents a great challenge for selective phagocytic activity
[28,65]. Moreover, the limited efficacy of conventional
anti-malarial drugs, resistance development, inhibitory effects, and
potential toxicities hinder effective macrophage-specific drug
delivery[81,82]. Overall, the complexity of phagocytic interactions
need for precise targeting, and limitations in studying these processes
pose significant obstacles in leveraging phagocytic activities for
effective malaria treatment[16,41,83].
This work focuses on enhancing the understanding of phagocytosis in
malaria immunity by discussing the recent and previous findings with
targeted investigations exploring the impact of effective cells, host
factors, and opsonin-like antibodies on parasite clearance. In addition,
The role of phagocyte subpopulations, specifically monocytes in
detecting and clearing infected erythrocytes (IEs) or parasite
molecules. Subsequent research should explore in more detail the
phagocytic mechanism on advanced cellular and molecular levels by
providing deeper insights into its protective and potentially harmful
effects. Additionally, the impact of merozoite antigens on the
phagocytic process can be stated by shedding light on potential targets
for controlling parasitemia and preventing clinical malaria.
Understanding the molecular pathways that influence the balance between
protection and pathology is crucial for developing novel antimalarial
therapies and informing vaccine designs.
The review article results may have a substantial influence on clinical
trials and subsequent research on malaria since it offers collective
findings on the relationship between the malaria parasite and the
phagocytic mechanism. The data generated may help create new treatment
approaches and vaccine designs that target certain immune evasion
pathways or enhance phagocytic activity by clarifying how P. falciparum
evades phagocytosis and the ensuing immunological response. This might
lead to more effective treatments and preventive measures, which could
enhance clinical trial results and hasten the fight to eradicate
malaria.
Conclusion
Exploring Phagocytic complex activities in P. falciparum infection
involves understanding the roles of different phagocytic cells,
interrelated factors, and their interactions with infected erythrocytes
(IEs) and parasite particles. The impact of phagocytosis on the overall
host protective immune response contributes substantially to the
elimination of infected cells and control of malaria infection. Quite a
perception of phagocytic immunomodulation and evasion strategies and
previous treatment implications is essential, and it can potentially
lead to the design of innovative therapeutic approaches to enhance
phagocytic activities and strengthen outcomes in malaria infections.
It is imperative to understand the immunological pathways and factors
affecting phagocytosis, including opsonins, distinct phagocyte
subpopulations, and inhibitory molecules, which represent a great
scientific and immunological challenge. Thus far, there is a need for
more comprehensive studies to address the complete spectrum of
phagocytic mechanisms involved in P. falciparum infections.